Extended-spectrum Cephalosporin Resistance Research Articles

2056. Trends in the Rates of Multidrug-resistant Bacteria Commonly Associated with Healthcare in U.S. Acute Care Hospitals, 2019-June 2021

Abstract Background Several studies demonstrated an increase in hospital-onset (HO) infections during the COVID-19 pandemic. We examined trends in the rates of multidrug-resistant (MDR) infections among acute care hospitals in the United States (U.S.) for bacteria commonly associated with healthcare: methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase production (ESBL), vancomycin resistant Enterococcus (VRE), MDR Pseudomonas aeruginosa, carbapenem resistant Enterobacteriaceae (CRE), and carbapenem-resistant Acinetobacter species (CRAB). Methods We measured incidence of clinical cultures yielding the bacterial species of interest among hospitalized patients in a dynamic cohort of hospitals submitting data to the Premier Healthcare Database Special COVID-19 Release during 2019-June 2021. Community-onset (CO) cultures were obtained ≤ day 3 of hospitalization; HO were obtained ≥ day 4. We determined monthly hospital-specific rates for each species. We used generalized estimating equations (GEE) multivariable negative binomial regression models adjusting for hospital characteristics to examine trends. Results From 2019-June 2021, the overall number of hospitals contributing data was 318. Rates for each pathogen are shown in Figures 1 and 2. All pathogens’ HO rates were significantly higher in 2021 compared with 2019. The rates of ESBL, VRE, and CRE were also significantly higher in 2021 when compared to 2020 (Table 1a). For CO rates, we found that MRSA rates decreased significantly during the study period, while ESBL, VRE, and CRE increased with varying degree of significance (Table 1b). Rates of CO MDR Pseudomonas and CO CRAB did not significantly change. Conclusion Our study confirmed that the rates of several MDR infections increased during the COVID-19 pandemic through June 2021, especially HO infections. CO MRSA was the only pathogen with consistent and significant decline. As infections caused by MDR pathogens represent a serious threat to patient safety, further study of factors contributing to the emerging trends may inform prevention strategies during a pandemic. Disclosures All Authors: No reported disclosures.

2050. Proportion of hospital-onset infections expressing antibiotic resistant (AR) phenotypes in US Hospitals, 2018 – 2020

Abstract Background Reports suggest the COVID-19 pandemic in 2020 was associated with increases in hospital-onset AR infections, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp., carbapenem-resistant Enterobacterales (E. coli, Klebsiella spp., and Enterobacter spp.) (CRE) and Acinetobacter spp. (CRAsp), extended-spectrum cephalosporin resistance suggestive of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), and multidrug-resistant Pseudomonas aeruginosa (MDR-PA). To evaluate whether trends were similar for susceptible and resistant strains, we estimated the proportions of these resistant phenotypes in U.S. hospitals. Figure 1.Proportion of hospital-onset pathogens expressing resistant phenotypes, 2018 – 2020 Methods We analyzed 2018–2020 hospital microbiology data in the Premier Healthcare and BD Insights Research Databases. Hospital-onset (HO) infections were those with positive cultures collected after hospital day 3. We used a raking procedure to produce weights to match national hospital characteristics, specifically: U.S. census division, bed size, teaching status, age, gender and urban/rural designation. We used a weighted means survey procedure for annual national estimates and generated annual comparisons with multivariable logistic regression adjusted by hospital characteristics. Results In 589 hospitals, the percentages of HO ESBL-E and CRAsp increased from 2019 to 2020 (Table). Among enterococci, the percentage with vancomycin resistance decreased. The percentages of MRSA, CRE, and MDR-PA did not change. Conclusion Our findings suggest pandemic-related factors, such as changes in antibiotic use or infection control, may have differentially affected susceptible and resistant phenotypes of hospital pathogens. Increases in the percentages of HO CRAsp and ESBL-E suggest these resistant phenotypes may have had a selective advantage over susceptible strains during the pandemic. In contrast, no changes in the percentages of HO MRSA or MDR-PA were observed, suggesting that infection rates increased similarly for resistant and susceptible strains. These findings underscore the importance of strategies to prevent hospital-associated infections and AR that are resilient to pandemic-related stresses on the healthcare system. Disclosures All Authors: No reported disclosures.

2229. Antibiotic Resistance in Gram-Negative Community-Onset Urinary Tract Infections Among Adults Presenting to Hospitals, United States, 2012-2020

Abstract Background Choosing empiric therapy for patients with community-onset urinary tract infections (CO-UTI) presenting to hospitals for treatment is challenging without understanding local antimicrobial susceptibility patterns. We investigated changes over time in antimicrobial resistance among CO-UTI pathogens and identified patient-level factors associated with higher levels of resistance. Methods We used non-duplicate positive urine cultures in the 2012-2020 Premier Healthcare Database as a proxy for CO-UTI in patients ≥ 18 years old presenting to hospitals receiving care categorized as community-onset inpatient (CO-INPT) or observation/emergency department (OBS/ED). We included cultures positive for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa obtained within 3 days of admission. Phenotypes investigated include resistance to extended-spectrum cephalosporins (ESC), fluoroquinolones (FLQ), and trimethoprim-sulfamethoxazole (TMP-SX). Logistic regression analyses were performed. Results Among 1,987,605 urine cultures meeting study criteria from 432 hospitals, > 66% were E. coli. Antibiotic resistance (AR) was highest to FLQ among CO-INPT E. coli (31.7%) and P. mirabilis (29.3%) in 2020. ESC resistance increased from 2012 to 2020 among E. coli and K. pneumoniae in both CO-INPT and OBS/ED (p< 0.001). TMP-SX resistance remained > 20% among E. coli in CO-INPT and OBS/ED and P. mirabilis in CO-INPT throughout the study period. All AR phenotypes were significantly higher among CO-INPT than OBS/ED (p< 0.001), and higher among males than females (p< 0.001). FLQ resistance among E. coli, P. mirabilis, and P. aeruginosa was > 20% among males (28.2%, 30.4%, 21.9% respectively) but not females (17.5%, 15.1%, 14.5%) in OBS/ED, while it was > 20% among both males (37.2%, 37.3%, 24.6%) and females (31.2%, 33.9%, 21.9%) in CO-INPT. Figure 1.% Resistance to extended-spectrum cephalosporins by year and acute care setting.Figure 2.% Resistance to fluoroquinolones by year and acute care setting.Figure 3.% Resistance to trimethoprim-sulfamethoxazole by year and acute care setting. Conclusion Resistance to TMP-SX in both CO-INPT and OBS/ED, and FLQ in CO-INPT, was elevated suggesting alternative empiric therapy might be necessary for CO-UTI presenting to hospitals. Increasing resistance to ESC among pathogens in CO-INPT cultures warrants further evaluation of local resistance levels. Gender and need for inpatient therapy are factors to consider in developing local treatment recommendations. Disclosures All Authors: No reported disclosures.

Dynamics of extended-spectrum cephalosporin resistance genes in Escherichia coli from Europe and North America

Extended-spectrum cephalosporins (ESCs) are critically important antimicrobial agents for human and veterinary medicine. ESC resistance (ESC-R) genes have spread worldwide through plasmids and clonal expansion, yet the distribution and dynamics of ESC-R genes in different ecological compartments are poorly understood. Here we use whole genome sequence data of Enterobacterales isolates of human and animal origin from Europe and North America and identify contrasting temporal dynamics. AmpC β-lactamases were initially more dominant in North America in humans and farm animals, only later emerging in Europe. In contrast, specific extended-spectrum β-lactamases (ESBLs) were initially common in animals from Europe and later emerged in North America. This study identifies differences in the relative importance of plasmids and clonal expansion across different compartments for the spread of different ESC-R genes. Understanding the mechanisms of transmission will be critical in the design of interventions to reduce the spread of antimicrobial resistance.

Molecular characterization of extended-spectrum cephalosporin and fluoroquinolone resistance genes in Salmonella and Shigella isolated from clinical specimens in Thailand

Antimicrobial resistance of Salmonella and Shigella has become a major clinical and public health problem. The incident of co-resistance to third generation cephalosporins and fluoroquinolone is a serious therapeutic issue in Thailand. The present study aimed to investigate the antimicrobial resistance and molecular character of clinical Shigella and Salmonella isolates. A total of 33 Salmonella and 53 Shigella cefotaxime-resistant isolates were collected from human clinical cases in Thailand during the period from 2011–2018. The antimicrobial susceptibility of Salmonella and Shigella was determined by the disk diffusion method, and extended-spectrum beta-lactamase (ESBL) production was characterized by the double-disk synergy test. Genotype characterization was performed by PCR and DNA sequencing. Thirty-two (97.0%) and fifty-two (98.1%) isolates of cefotaxime-resistant Salmonella and Shigella, respectively, were identified as ESBL producers. Shigella sonnei (4 isolates), Salmonella serovar 4,5,12:i:- (6 isolates), Salmonella serovar Agona (2 isolates) and Salmonella serovar Rissen (2 isolates) showed co-resistance to ciprofloxacin and cefotaxime or ceftriaxone. The combination of blaCTX-M-15 plus other ESBL and/or AmpC β-lactamase genes was the most dominant of the genotype patterns in ESBL-producing isolates. The plasmid harbouring the aac(6′)-Ib-cr gene and mutations of gyrA (S83F, D87Y or D87G) and parC (T57S) genes was found in 2 ESBL-producing Salmonella isolates. Three Shigella sonnei isolates harboured mutations in gyrA (S83L, D87Y or D87G), and only one Shigella sonnei phase I isolate showed mutations in both gyrA (S83L and D87G) and parC (S80I) genes. Among these clinical Shigella sonnei isolates, qnrS determinants were identified. Production of ESBLs is an important mechanism for resistance to extended-spectrum cephalosporins in Salmonella and Shigella. The emergence of a decreased susceptibility to extended-spectrum cephalosporins and fluoroquinolone in ESBL-producing isolates has important clinical and therapeutic implications.

Clonal Dissemination of Extended-Spectrum Cephalosporin-Resistant Enterobacterales between Dogs and Humans in Households and Animal Shelters of Romania.

Faecal carriage of extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales in healthy pets is a concerning issue. This study aimed to determine the prevalence, genetic background, and potential for interspecies transmission of these bacteria between dogs and humans within the same household (HH) or shelter environment in Romania. Faecal samples (n = 263) collected from healthy dogs (n = 102), their owners (n = 32), as well as dogs (n = 110) and staff (n = 19) from dog shelters, were screened for ESC-R carriage. Clonal relatedness of canine and human Escherichia coli isolates was established using Fourier Transform Infrared Spectroscopy (FTIR), followed by Illumina WGS of selected isolates. The highest prevalence of ESC-R Enterobacterales faecal carriage was identified in staff working at dog shelters (78.9%), followed by dogs from households (44.11%), dog owners (43.7%), and dogs from shelters (27%). FTIR identified 15 clusters of closely related E. coli isolates, including dog and human isolates from the same environment. Co-carriage of ESC-R isolates in both the dog and owner was identified in 12 HHs (37.5%), with two HHs (6%) having both the owner and dog carrying isolates with identical FTIR spectra, phylogroup, resistance genes, and Inc plasmids. Major ExPEC lineages such as ST127, ST10, ST155, and ST88 were detected in human and dog isolates. Our study revealed a high prevalence of faecal ESC-R E. coli carriage in both dogs and humans from Romanian households and shelters, where bidirectional clonal transmission between humans and dogs is likely. Furthermore, we identified ESC-R Enterobacterales co-carriage in people and dogs sharing the same environment using FTIR, demonstrating its value in AMR surveillance for humans and animals.

Air temperature and incidence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae

BackgroundHigher outdoor temperature may be related to an increase in antibiotic resistant bacteria. We investigated the association between local outdoor air temperature and the incidence of extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) correcting for known drivers of antibiotic resistance. MethodsWe performed a time-series regression study using prospectively collected weekly surveillance data on all ESBL-PE isolated from in- and outpatients of the University Hospital Basel, a tertiary care center in Switzerland, between 01/2008–12/2017. Temperature was measured hourly at the meteorological institute of the University Basel next to our institution over this time period. A time-series approach using a Poisson regression model and different lag terms for delayed exposure effects was performed to assess associations between minimal, mean and maximal weekly temperature and the number of ESBL-PE recovered. ResultsOver 10 years, recovery of ESBL-PE increased (annual incidence rate ratio [IRR] 1.14, 95%CI 1.13–1.16), while mean weekly temperature measures remained stable. In multivariable analyses, increasing temperature was associated with higher recovery rates of ESBL-PE after three to four weeks, correcting for potential confounders, such as the number of admissions, proportion of long-term nursing facility- and ICU-admissions, age, Charlson comorbidity index and consumption of antimicrobials (IRRs per 10 °C ranging from 1.14 to 1.22, 95%CIs 1.07–1.33). These trends remained when analyzing correlations between temperature with the proportion of extended spectrum cephalosporin resistance of all recovered Enterobacteriaceae. ConclusionsHigher outdoor temperature may be associated with an increase of ESBL-PE-incidence, independent of important confounders, such as antimicrobial consumption and thus should be considered for future resistance-trajectories.

THE GLOBAL SPREAD AND EPIDEMIOLOGICAL CHARACTERISTICS OF SALMONELLA SPP, ESCHERICHIA COLI AND METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA):RELATED RESEARACH STUDIES IN SERBIA

It has been established that some clones of pathogenic bacteria such as Salmonella spp., Escherichia coli ST131, and methicillin-resistant Staphylococcus aureus (MRSA) tend to spread worldwide. Therefore, epidemiological surveys have been conducted to identify the source of infection and to break the chain of infection. In this article, it was pointed out that common international clones of Salmonella are represented with the serotypes Typhimurium, Kentucky, Infantis and Enteritidis. Serovars Typhimurium and Kentucky display multidrug-resistant phenotypes more frequently. Several sequence types of E. coli and the international clone ST131 are described, including clades C1 and C2 with the extended-spectrum cephalosporin-resistance genes (blaCTX-M-15 or blaCTX-M-27). These pathogens are often found in both humans and animals. It is noted that Staphylococcus aureus became resistant to methicillin almost instantly after its introduction into clinical practice. Soon afterwards, MRSA found its way to farm animals and wildlife. The cycles of infection are bidirectional: humans can disseminate MRSA in the environment but animals may also be sources of infection for humans. Comprehensive work has been done by epidemiologists to introduce all necessary measures to eliminate MRSA from hospitals. Also, much effort has been made in MRSA control to prevent infections on animal farms and contamination in the primary food production chain. As the struggle with pathogenic bacteria continues, we face the incessant threat of new resistance and virulence mechanisms, which bacteria use to resist the hostile environment and enhance their survival in their natural habitats including humans and animals. Therefore, the capacity of certain bacteria to spread due to their virulence mechanisms and resistance phenotypes is presented, and a brief description of the research conducted in Serbia is included.

Longitudinal study on the prevalence of extended spectrum cephalosporins-resistant Escherichia coli colonization in Dutch veal farms

A longitudinal study was performed to investigate the prevalence of Extended-Spectrum Cephalosporin-Resistant (ESC-R) Escherichia coli colonization in Dutch veal farms. Rectal swabs from 683 calves born in 13 Dutch dairy farms were collected one day prior to transportation to the veal farm at 14 or 28 days of age, and at 5 different time points 8 Dutch veal farms. In addition, characteristics of the calf, cows, and farm management were collected. Rectal swabs were selectively cultured for ESC-R E. coli. In total, 1202 ESC-R E. coli isolates were recovered. Overall, the prevalence of ESC-R E. coli increased from 24.4 % at one day prior to transportation to 57.3 % in week two after arrival of calves at the veal farm. No associations were found between the presence of ESC-R E. coli at the dairy or veal farm and age of transportation, sex and breed. The presence of ESC-R E. coli in week 6, 10, and 18 at the veal farm was positively associated with the presence of ESC-R E. coli in week 10, 18, and 24, respectively (p < 0.05). Individual antibiotic treatments applied before week 2 and 6 upon arrival to the veal farms tended to increase the ESC-R E. coli colonization frequency. Our results indicate that ESC-R E. coli colonization frequency substantially increases after arrival of calves on the veal farm. In addition to individual antibiotic treatments, it is considered likely that frequently applied batch antibiotic treatments are also implicated in the ESC-R E. coli colonization frequency.

In vitro selection of Neisseria gonorrhoeae unveils novel mutations associated with extended-spectrum cephalosporin resistance.

The emergence of Neisseria gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESCs) is a worldwide concern because this class of antibiotics represents the last empirical treatment option for gonorrhea. The abusive use of antimicrobials may be an essential factor for the emergence of ESC resistance in N. gonorrhoeae. Cephalosporin resistance mechanisms have not been fully clarified. In this study, we mapped mutations in the genome of N. gonorrhoeae isolates after resistance induction with cefixime and explored related metabolic pathways. Six clinical isolates with different antimicrobial susceptibility profiles and genotypes and two gonococcal reference strains (WHO F and WHO Y) were induced with increasing concentrations of cefixime. Antimicrobial susceptibility testing was performed against six antimicrobial agents before and after induction. Clinical isolates were whole-genome sequenced before and after induction, whereas reference strains were sequenced after induction only. Cefixime resistance induction was completed after 138 subcultures. Several metabolic pathways were affected by resistance induction. Five isolates showed SNPs in PBP2. The isolates M111 and M128 (ST1407 with mosaic penA-34.001) acquired one and four novel missense mutations in PBP2, respectively. These isolates exhibited the highest minimum inhibitory concentration (MIC) for cefixime among all clinical isolates. Mutations in genes contributing to ESC resistance and in other genes were also observed. Interestingly, M107 and M110 (ST338) showed no mutations in key determinants of ESC resistance despite having a 127-fold increase in the MIC of cefixime. These findings point to the existence of different mechanisms of acquisition of ESC resistance induced by cefixime exposure. Furthermore, the results reinforce the importance of the gonococcal antimicrobial resistance surveillance program in Brazil, given the changes in treatment protocols made in 2017 and the nationwide prevalence of sequence types that can develop resistance to ESC.

Molecular characterization of extended spectrum cephalosporin resistant Escherichia coli isolated from livestock and in-contact humans in Southeast Nigeria.

The rise in antimicrobial resistance (AMR) in bacteria is reducing therapeutic options for livestock and human health, with a paucity of information globally. To fill this gap, a One-Health approach was taken by sampling livestock on farms (n = 52), abattoir (n = 8), and animal markets (n = 10), and in-contact humans in Southeast Nigeria. Extended spectrum cephalosporin (ESC)-resistant (ESC-R) Escherichia coli was selectively cultured from 975 healthy livestock faecal swabs, and hand swabs from in-contact humans. Antimicrobial susceptibility testing (AST) was performed on all ESC-R E. coli. For isolates showing a multi-drug resistance (MDR) phenotype (n = 196), quantitative real-time PCR (qPCR) was performed for confirmation of extended-spectrum β-lactamase (ESBL) and carbapenemase genes. Whole-genome sequencing (WGS) was performed on a subset (n = 157) for detailed molecular characterisation. The results showed ESC-R E. coli was present in 41.2% of samples, with AST results indicating 48.8% of isolates were phenotypically MDR. qPCR confirmed presence of ESBL genes, with blaCTX-M present in all but others in a subset [blaTEM (62.8%) and blaSHV (0.5%)] of isolates; none harboured transferable carbapenemase genes. Multi-locus sequence typing identified 34 Sequence Types (ST) distributed among different sampling levels; ST196 carrying blaCTX-M-55 was predominant in chickens. Large numbers of single nucleotide polymorphisms (SNPs) in the core genome of isolates, even within the same clade by phylogenetic analysis, indicated high genetic diversity. AMR genotyping indicated the predominant blaCTX-M variant was blaCTX-M-15 (87.9%), although blaCTX-M-55, blaCTX-M-64, and blaCTX-M-65 were present; it was notable that blaCTX-M-1, common in livestock, was absent. Other predominant AMR genes included: sul2, qnrS1, strB, blaTEM-1b, tetA-v2, and dfrA14, with prevalence varying according to host livestock species. A blaCTX-M-15 harbouring plasmid from livestock isolates in Ebonyi showed high sequence identity to one from river/sewage water in India, indicating this ESBL plasmid to be globally disseminated, being present beyond the river environment. In conclusion, ESC-R E. coli was widespread in livestock and in-contact humans from Southeast Nigeria. WGS data indicated the isolates were genetically highly diverse, probably representing true diversity of wild type E. coli; they were likely to be MDR with several harbouring blaCTX-M-15. Surprisingly, human isolates had highest numbers of AMR genes and pigs the least.

Resistance to extended-spectrum cephalosporins in Escherichia coli and Salmonella enterica isolated from food-producing animals: Ecological study from selected national surveillance programs

Extended-spectrum cephalosporins (ESC) are categorized by World Health Organization as critically important antimicrobials with limited therapeutic alternatives for the treatment of severe bacterial infections in humans. Preserving the effectiveness of ESC requires continuous monitoring of resistance and comparison of associated data across national surveillance programs in the face of globalization. In this ecological study, we compared ESC resistance in Escherichia coli and Salmonella enterica isolated from food-producing animals from 2003 to 2019 between nine countries (Canada, Denmark, Finland, Japan, Netherlands, Norway, Sweden, United Kingdom, and the United States). Using the beta-regression model, compared to Canada, non-selective ESC-R Salmonella enterica was less likely isolated from food producing animals in other eight countries (Odds ratio range: 0.07–0.76). We observed an interaction between the country and the year with a significantly decreased proportion (P < 0.05) of non-selective ESC-R Escherichia coli from the Netherlands, the United Kingdom, and the United States compared to Canada over the years. There was a linear correlation between non-selective ESC-R Escherichia coli and ESC use from Netherlands (Spearman’s ρ = 0.91, P < 0.0001). For the six European countries, the interaction between the country and year showed a significant decrease in the proportion of selective ESC-R Escherichia coli over the years for the Netherlands compared to Denmark (P = 0.002). While there were variations in the proportion of beta-lactamase genes reported over the years, blaCTX-M and blaCMY-2 genes were commonly detected among the selective ESC-R Escherichia coli. This study reveals variability in the recovery of ESC-resistant bacteria among the countries that seems likely influenced by the individual country policy on the use of critically important antimicrobials and resistance surveillance programs. However, there is a need for harmonization and consistency in food animal sources of bacterial isolates used in surveillance programs within and between the countries for easy comparability.

Trends in DTR, CR, ECR, and FQR in Four Common Gram-Negative Bacteria: A Retrospective Study from 2013 to 2021.

PurposeThe purpose of this study was to examine the prevalence of four important drug-resistance phenotypes: difficult-to-treat resistance (DTR), fluoroquinolone resistance (FQR), carbapenem resistance (CR), and extended-spectrum cephalosporin resistance (ECR).MethodsDTR was defined as insensitivity to all the β-lactams and fluoroquinolones tested. We retrospectively analyzed the distribution characteristics of specific drug-resistant phenotypes of the main Gram-negative bacteria causing bloodstream infections (BSIs) in Tongji Hospital (Wuhan, China) between 2013 and 2021: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii.ResultsFQR was the main antimicrobial resistance phenotype of E. coli, accounting for 59.45% (1117/1879, 95% confidence interval, 57.21%–61.65%); the detection rates for CR and DTR were low, accounting for 1.86% (35/1879, 1.34%–2.58%), and 1.81% (34/1879, 1.30%–2.52%), respectively. However, the detection rates for CR and DTR in K. pneumoniae were 38.83% (497/1280, 36.20%–41.53%) and 35.94% (460/1280, 33.35%–38.60%), respectively. In P. aeruginosa, the detection rates of the four drug-resistant phenotypes (DTR, CR, FQR, and ECR) were all < 30%, but conversely, for A. baumannii, the detection rates were all > 80%. The changes in the data from 2013 to 2021 showed upward trends (z > 0) for CR-E. coli, DTR-E. coli, FQR-E. coli, CR-K. pneumoniae, DTR-K. pneumoniae, FQR-K. pneumoniae, and ECR-K. pneumoniae, but downward trends (z < 0) for ECR-E. coli, CR-A. baumannii, DTR-A. baumannii, FQR-A. baumannii, ECR-A. baumannii, CR-P. aeruginosa, DTR-P. aeruginosa, FQR-P. aeruginosa, and ECR-P. aeruginosa.ConclusionDTR warrants further attention, especially in in BSI-associated K. pneumoniae and A. baumannii, in which the detection rates were very high. Between 2013 and 2021 in this region, DTR-E. coli and CR-E. coli showed obvious upward trends, whereas DTR-P. aeruginosa and ECR-P. aeruginosa showed obvious downward trends.

What Doesn't Kill Them Makes Them Stronger: The Impact of the Resistance Patterns of Urinary Enterobacterales Isolates in Patients from a Tertiary Hospital in Eastern Europe.

(1) Background: The evolution of bacterial resistance to antibiotics is one of the factors that make infectious pathology an extremely dynamic field, also inducing a significant burden on public health systems; therefore, continuous updates on the bacterial resistance to antibiotics and their particular regional patterns is crucial for the adequate approach of various infectious diseases. (2) Methods: We retrospectively analyzed 354 patients with Enterobacterales urinary tract infections (UTIs), determined their antibiotic resistance pattern, thus aiming to correlate them with the outcome and other specific markers of poor prognosis. (3) Results: The most frequent causative agent was Escherichia coli, representing 64.6% of all UTIs. We identified 154 patients resistant to multiple antibiotic classes, of which 126 were multidrug-resistant (MDR), 17 were extensive drug-resistant (XDR) and 11 were pandrug-resistant (PDR). Moreover, 25 isolates were resistant to carbapenems (CRE), 25 were difficult-to-treat (DTR), and 84 were extended-spectrum cephalosporin-resistant (ESC), with only 95 isolates susceptible to all tested antibiotics. Mortality ranged from 1% for UTIs caused by isolates susceptible to all tested antibiotics, to 24% for the ones caused by DTR or CRE isolates. Other significant risk factors associated with mortality were: prolonged hospital stay (p = 0.0001), Charlson comorbidity index ≥ 3 (p = 0.02), urinary catheterization (p = 0.001), associated respiratory pathologies (p = 0.004), obesity (p = 0.047), a history of previous hospitalizations (p = 0.007), inappropriate empiric antibiotic regimen (p = 0.001), or hyper inflammatory status (p = 0.006). Basically, we observed that a multiple regression model comprising urinary catheterization, inappropriate empiric anti-biotherapy, obesity, and respiratory comorbidities exhibits the best correlation with mortality rate in patients with UTI (R = 0.347, R2 = 0.12). (4) Conclusions: By focusing on the novel resistance patterns, our study provides complementary evidence concerning the resistance profiles found in an Eastern European region, as well as their prognostic implications in patients with UTI.

Markedly Increasing Antibiotic Resistance and Dual Treatment of Neisseria gonorrhoeae Isolates in Guangdong, China, from 2013 to 2020.

The emergence of multidrug resistance in Neisseria gonorrhoeae is concerning, especially the cooccurrence of azithromycin resistance and decreased susceptibility to extended-spectrum cephalosporin. This study aimed to confirm the antibiotic resistance trends and provide a solution for N. gonorrhoeae treatment in Guangdong, China. A total of 5,808 strains were collected for assessment of antibiotic MICs. High resistance to penicillin (53.80 to 82%), tetracycline (88.30 to 100%), ciprofloxacin (96 to 99.8%), cefixime (6.81 to 46%), and azithromycin (8.60 to 20.03%) was observed. Remarkably, spectinomycin and ceftriaxone seemed to be the effective choices, with resistance rates of 0 to 7.63% and 2.00 to 16.18%, respectively. Moreover, the rates of azithromycin resistance combined with decreased susceptibility to ceftriaxone and cefixime reached 9.28% and 8.64%, respectively. Furthermore, genotyping identified NG-STAR-ST501, NG-MAST-ST2268, and MLST-ST7363 as the sequence types among representative multidrug-resistant isolates. Evolutionary analysis showed that FC428-related clones have spread to Guangdong, China, which might be a cause of the rapid increase in extended-spectrum cephalosporin resistance currently. Among these strains, the prevalence of N. gonorrhoeae was extremely high, and single-dose ceftriaxone treatment might be a challenge in the future. To partially relieve the treatment pressure, a susceptibility test for susceptibility to azithromycin plus extended-spectrum cephalosporin dual therapy was performed. The results showed that all the representative isolates could be effectively killed with the coadministration of less than 1 mg/liter azithromycin and 0.125 mg/liter extended-spectrum cephalosporin, with a synergistic effect according to a fractional inhibitory concentration (FIC) of <0.5. In conclusion, dual therapy might be a powerful measure to treat refractory N. gonorrhoeae in the context of increasing antibiotic resistance in Guangdong, China.

In Vitro Demonstration of Targeted Phage Therapy and Competitive Exclusion as a Novel Strategy for Decolonization of Extended-Spectrum-Cephalosporin-Resistant Escherichia coli.

Extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli have disseminated in food-producing animals globally, attributed to horizontal transmission of blaCTX-M variants, as seen in the InCI1-blaCTX-M-1 plasmid. This ease of transmission, coupled with its demonstrated long-term persistence, presents a significant One Health antimicrobial resistance (AMR) risk. Bacteriophage (phage) therapy is a potential strategy in eliminating ESC-R E. coli in food-producing animals; however, it is hindered by the development of phage-resistant bacteria and phage biosafety concerns. Another alternative to antimicrobials is probiotics, with this study demonstrating that AMR-free commensal E. coli, termed competitive exclusion clones (CECs), can be used to competitively exclude ESC-R E. coli. This study isolated and characterized phages that lysed E. coli clones harboring the InCI1-blaCTX-M-1 plasmid, before investigation of the effect and synergy of phage therapy and competitive exclusion as a novel strategy for decolonizing ESC-resistant E. coli. In vitro testing demonstrated superiority in the combined therapy, reducing and possibly eliminating ESC-R E. coli through phage-mediated lysis coupled with simultaneous prevention of regrowth of phage-resistant mutants due to competitive exclusion with the CEC. Further investigation into this combined therapy in vivo is warranted, with on-farm application possibly reducing ESC-R prevalence, while constricting newly emergent ESC-R E. coli outbreaks prior to their dissemination throughout food-producing animals or humans. IMPORTANCE The emergence and global dissemination of resistance toward critically important antimicrobials, including extended-spectrum cephalosporins in the livestock sector, deepens the One Health threat of antimicrobial resistance. This resistance has the potential to disseminate to humans, directly or indirectly, nullifying these last lines of defense in life-threatening human infections. This study explores a novel strategy, the coadministration of bacteriophages (phages) and a competitive exclusion clone (antimicrobial-susceptible commensal E. coli), to revert an antimicrobial-resistant population to a susceptible population. While phage therapy is vulnerable to the emergence of phage-resistant bacteria, no phage-resistant bacteria emerged when a competitive exclusion clone was used in combination with the phage. Novel strategies that reduce the prevalence and slow the dissemination of extended-spectrum cephalosporin-resistant E. coli in food-producing animals have the potential to extend the time frame in which antimicrobials remain available for effective use in animal and human health.

Microbiological and clinical changes following the transition to the 2010 revised CLSI breakpoints for extended-spectrum cephalosporin in Enterobacterales

In 2016, our laboratory adopted the 2010 CLSI extended-spectrum cephalosporins (ESC) breakpoint criteria in Enterobacterales. ESBL testing had continued in Blood cultures but discontinued in General Cultures. The aims of this study were to examine the effect of this transition on (1) the resistance rates to ESC; (2) the consumption of parenteral β-lactam antimicrobials, and (3) the therapeutic use of ESC and the outcome of patients infected by ESBL-producing Enterobacterales. In K. pneumoniae and E. coli, the ESC resistance rates had increased, declined or remained unchanged in Urine, General and Blood cultures, respectively. In P. mirabilis, the resistance rates declined for ceftazidime but remained unchanged for ceftriaxone. Carbapenem consumption had not replaced ESC, but the consumption of piperacillin-tazobactam had increased. The use of ESC in suspected ESBL infections had increased slightly, without effect on clinical outcome.

Antimicrobial Resistance Among Pathogens Causing Bloodstream Infections: A Multicenter Surveillance Report Over 20 Years (1998-2017).

PurposeBloodstream infections (BSIs) are a common consequence of infectious diseases and cause high morbidity and mortality. Appropriate antibiotic use is critical for patients’ treatment and prognosis. Long-term monitoring and analysis of antimicrobial resistance are important in guiding physicians to choose appropriate antibiotics and understand the changes in antimicrobial resistance and infection control. Here, we report a retrospective study on the trends of antimicrobial resistance in the common BSI-associated pathogens.MethodsThe identification of strains and antimicrobial susceptibility tests were performed in each anticipating hospital independently. Data from the Hubei Province Antimicrobial Resistance Surveillance System (HBARSS) from 1998 to 2017 were retrospectively analyzed using WHONET 5.6 software.ResultsData from HBARSS (1998–2017) revealed that 40,518 Gram-positive bacteria and 26,568 Gram-negative bacteria caused BSIs, the most common of which were Staphylococcus aureus and Escherichia coli. Salmonella typhi was a predominant BSI-associated pathogen in 1998–2003. Antimicrobial susceptibility data showed that the resistance rates of E. coli and Klebsiella pneumoniae to cefotaxime were significantly higher than those to ceftazidime. The proportion of strains of special antimicrobial resistance phenotypes including difficult-to-treat resistance (DTR), carbapenem-resistant (CR), extended-spectrum cephalosporin resistant (ECR) and fluoroquinolone resistant (FQR) in E. coli was 0.18%, 0.26%, 13.95%, 22.78% while in K. pneumoniae was 11.95%, 14.00%, 31.91% and 11.40%, respectively. In 2013–2017, K. pneumoniae showed resistance levels reaching 15.8% and 17.5% to imipenem and meropenem, respectively, and Acinetobacter baumannii showed high resistance rates ranging from 60 to 80% to common antibiotics. The detection rate of Salmonella typhi resistance to third-generation cephalosporins and fluoroquinolones was less than 5%. Control of methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge, and in 2009–2017, the MRSA detection rate was 40–50%.ConclusionPrevalence of CR K. pneumoniae has increased significantly in recent years. Resistance rates of A. baumannii to common antimicrobial agents have increased exponentially, reaching high levels. MRSA remains a challenge to control. For K. pneumoniae, DTR, CR, ECR and FQR were antimicrobial resistance phenotypes that could not be ignored while for E. coli DTR and CR were rare antimicrobial resistance phenotypes. CR K. pneumoniae, A. baumannii and MRSA present major challenges for controlling BSIs.

Longitudinal Sampling Reveals Persistence of and Genetic Diversity in Extended-Spectrum Cephalosporin-Resistant Escherichia coli From Norwegian Broiler Production.

There are knowledge gaps concerning dynamics of extended-spectrum cephalosporin (ESC)-resistant Escherichia coli and their plasmids in broiler production and the persistence of strains on broiler farms. Thus, we aimed at characterising ESC-resistant Escherichia coli collected from all flocks reared on 10 different farms during a six-months sampling period. All isolates (n = 43) were subjected to whole-genome sequencing, and a subset of isolates (n = 7) were also sequenced using oxford nanopore technology and subsequent hybrid assembly in order to do in-depth characterisation of the ESC resistance plasmids. The 43 isolates belonged to 11 different sequence types, and three different ESC resistance gene/plasmid combinations were present, namely, IncK2/blaCMY-2 (n = 29), IncI1/blaCMY-2 (n = 6) and IncI1/blaCTX-M-1 (n = 8). ESC-resistant E. coli of different STs and with different ESC resistance gene/plasmid combinations could be present on the same farm, while a single ST and ESC resistance gene/plasmid displaying zero or few SNP differences were present on other farms. In-depth characterisation of IncK2/blaCMY-2 plasmids revealed that at least two distinct variants circulate in the broiler production. These plasmids showed close homology to previously published plasmids from other countries. Our longitudinal study show that ESC-resistant E. coli belong to a multitude of different STs and that different ESC resistance genes and plasmids occur. However, there is also indication of persistence of both ESC-resistant E. coli strains and IncK2/blaCMY-2 plasmids on farms. Further studies are warranted to determine the dynamics of strains, plasmids and ESC resistance genes within single broiler flocks.

1277. Colonization Rates for Antimicrobial-resistant Bacteria in Kenya: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study

BackgroundCharacterization of antimicrobial-resistant organism (ARO) colonization is critical to understand transmission dynamics and infection risk, however data in resource-limited settings are scare. We estimated the prevalence of Enterobacterales colonization with extended-spectrum cephalosporin-resistance (ESCrE), carbapenem-resistance (CRE) and methicillin-resistant Staphylococcus aureus (MRSA) among community residents and hospitalized patients in rural (Siaya County) and urban (Kibera) Kenya.MethodsCommunity-dwelling adults and children were enrolled via cluster randomized sampling. Inpatients of all ages were enrolled by simple random sampling. Stool/rectal and nasal swabs were collected and screened for ESCrE, CRE and MRSA, respectively, using HardyChrom™ media. Vitek2® was used for isolate confirmation and antibiotic susceptibility testing. Fisher’s exact tests were used to compare prevalence of AROs.ResultsThe prevalence of ESCrE was higher for the urban hospital (69.8%, 263/377) compared to rural hospitals (62.7%, 298/475, P=0.04); a similar pattern was evident for CRE (16.7%, 63/377 and 6.5%, 31/475, respectively, P< 0.01). The prevalence of MRSA was 3.2% for both urban and rural hospitals (P=0.99). For adults, the prevalence of ESCrE was higher in Kibera households (51.4%, 346/673) compared to Siaya (44.6%, 283/634, P=0.02) while the prevalence of both CRE and MRSA was < 3% for both areas and did not differ significantly (CRE, P=0.13, MRSA, P=0.14). There was no significant difference between urban and rural children for ESCrE (47.7%, 74/155 and 53.4%, 135/253, P=0.31); both CRE and MRSA were rarely detected (< 2%) with no difference across settings (CRE, P=1.0, MRSA, P=0.42). Among Enterobacteriaceae recovered, Escherichia coli and Klebsiella spp. predominated.ConclusionColonization with AROs were widespread in households and hospitals in urban and rural areas. Hospitals with elevated prevalence of highly transmissible AROs should consider whether implementation of colonization screening can be incorporated as part of their infection prevention and control programs. Risk factors for ARO colonization should be elucidated to identify novel prevention strategies.Disclosures All Authors: No reported disclosures