Extended-spectrum Cephalosporins Research Articles

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.

1196. Environmental Contamination of Rooms of Patients Harboring Multidrug-Resistant Organisms

Abstract Background Healthcare environmental contamination by patients harboring multidrug-resistant organism (MDROs) is an important source of hospital MDRO transmission. We aimed to determine the MDRO contamination and bioburden of surfaces within hospital rooms of patients with positive MDRO clinical cultures. Methods Patients with positive clinical cultures of MDROs (carbapenem resistant Acinetobacter baumannii [CRAB], carbapenem resistant Pseudomonas aeruginosa [CRPA], extended spectrum cephalosporin and carbapenem resistant Enterobacterales [ESCRE, CRE] and vancomycin resistant Enterococcus [VRE]) were identified through daily screening of clinical microbiology results. Patient peri-rectal, inguinal, and wound sampling was performed. E-swab and environmental sampling of room surface composites was performed using environmental sponge wipes. Composite 1 included the TV remote, telephone, call button and bed rails. Composite 2 included the room door handle, IV pole and overbed table. Composite 3 included toileting surfaces. Each composite surface area was no more than 350mm3 each. Sponge wipes were expressed in phosphate-buffered saline containing 0.1% Tween 20 using a stomacher. The eluate was concentrated removed leaving ∼ 5mL, and remaining resuspended by vortex. Undiluted suspension was plated on selective MDRO medias and broth. Microbial burden was calculated by summing composites bioburdens. Samples that were only broth positive were given a value of 1 CFU. Table 1.Demographic and Clinical Characteristics of Multidrug-resistant Organisms Positive Patients (n=5)Abbreviation: CRAB: carbapenem-resistant Acinetobacter baumanii, CRPA: carbapenem-resistant Pseudomonas aeruginosa, ESCRE: extended spectrum cephalosporin-resistant Enterobacterales, ESLD: end-stage liver disease, IBD: inflammatory bowel diseases, HTN: hypertension, MDRO: multidrug resistant organism, TBI: traumatic brain injury, VRE: vancomycin resistant enterococcus1- Immunosuppressed defined as solid organ transplant, bone marrow transplant within 12 months, chemotherapy within 6 months, HIV and CD4 <200, any immunomodulatory agent within the past 30 days, at least 10 mg of corticosteroid for >14 daysTable 2.Multidrug-resistant Organism Environmental Contamination and Bioburden of Patients and Environmental CompositesAbbreviation: CRAB: carbapenem-resistant Acinetobacter baumannii, CRPA: carbapenem-resistant Pseudomonas aeruginosa, ESCRE: extended spectrum cephalosporin-resistant Enterobacterales, VRE: vancomycin resistant Enterococcus, ND: not done, NG: no growth, N/A; not applicable1Patient Swab P1: peri-rectal, P2: wound or tracheostomy, P3: inguinal2Environmental Swab C1: TV remote, telephone, call button and bed rails; Composite 2 room door handle, IV pole and overbed table; Composite 3: toileting surfaces Results Five patients were included with target MDROs (1 CRAB, 1 CRPA, 2 ESCRE, 1 VRE). Demographic, clinical, and microbiological characteristics are summarized in Table 1. The same MDRO was detected in the environment of 60% (3/5) patients. Additional MDROs other than the clinical culture were cultured from patient and composite sites swabs (Table 2). Antibiotic susceptibility data confirmed similarity between patient and environmental isolates and identified additional MDROs present (Table 3,4). Additional patient enrollment and WGS isolates from clinical culture, patient and environmental isolates is ongoing. Table 3.Antimicrobial Susceptibility Profile of Isolates from Patients with Concordant Clinical and Environmental MDROsAbbreviation: CRAB: carbapenem-resistant Acinetobacter baumannii, ESCRE: extended spectrum cephalosporin-resistant Enterobacterales, MIC: minimum inhibitory concentration, N/A; not applicableTable 4.Antimicrobial Susceptibility Profile of Concordant Clinical and Environmental MDROsAbbreviation: CRAB: carbapenem-resistant Acinetobacter baumannii, MIC: minimum inhibitory concentration, N/A; not applicable, VRE: vancomycin resistant enterococcus Conclusion Concordance of clinical isolates with environmental isolates suggest that decolonization interventions could reduce environmental bioburden Disclosures All Authors: No reported disclosures.

1831. Longitudinal Changes in Antimicrobial-resistant Bacterial Bloodstream Infections in the US Military Health System from 2010-2019

Abstract Background The epidemiology of antibiotic-resistant pathogens guides antimicrobial therapy for bacterial bloodstream infections (BSI). We describe changes in antimicrobial-resistant BSI pathogens over time within the US Military Health System (MHS), which prospectively captures clinical and microbiological data from both retired and active-duty US Uniformed service members and their beneficiaries. Methods The study population included MHS beneficiaries with blood cultures positive for any bacterial pathogens (Jan 2010 – Dec 2019). Microbiological data were obtained from the Navy and Marine Corps Public Health Center and antibiotic resistance was interpreted using CLSI breakpoints corresponding to collection year. Blood contaminants were excluded. Difficult to treat resistance (DTR) was defined in Gram-negative bacteria (GNB) as isolates with in vitro resistance to three classes of antibiotics: carbapenems, extended-spectrum cephalosporins, and fluoroquinolones. Results The 15 most frequent bacterial pathogens, representing 15,358 BSI episodes from 12,749 individuals, were subcategorized in four groups based on shared BSI clinical features. Lactose-fermenting GNB (LFGNB) were most common, accounting for 42% of BSI pathogens, following by Streptococcus/Enterococcus spp. (33%), Staphylococcus aureus (20%), and non-lactose fermenting GNB (NLGNB, 5.5%). The rate of LFGNB BSI increased from 7.57 per 100,000 beneficiaries in 2010 to 8.42 in 2019 (peak of 8.83 in 2016), resulting in an increase of 11.3% during the study period (Figure). Rates of BSI attributed to Streptococcus/Enterococcus spp., S. aureus, and NLGNB decreased 26%, 29%, and 45%, respectively, over the study period. The average annual rates of methicillin-resistant S. aureus, vancomycin-resistant Enterococcus spp., and DTR GNB BSI were 1.30, 0.25, and 0.05 per 100,000 beneficiaries, respectively. Over the study period, these rates decreased 58.3%, 72.4% and 24.2%, respectively. Conclusion LFGNB BSI numerically increased over time while NLGNB BSI (e.g., Pseudomonas aeruginosa and Acinetobacter spp.) decreased. The burden of DTR GNB BSI also decreased, indicating that first-line antibiotics remain clinically available for most patients with BSI. Disclosures John H. Powers, III, MD, Arrevus: Advisor/Consultant|Eicos: Advisor/Consultant|Evofem: Advisor/Consultant|Eyecheck: Advisor/Consultant|Gilead: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|OPKO: Advisor/Consultant|Resolve: Advisor/Consultant|Romark: Advisor/Consultant|SpineBioPharma: Advisor/Consultant|UTIlity: Advisor/Consultant|Vir: Advisor/Consultant.

653. Characterizing Antibacterial Regimen Modification, Patient Characteristics, and Outcomes for Patients with Complicated Gram-negative Bacterial Infections

Abstract Background There are few studies describing the rationale or frequency of empiric or directed therapy treatment modification behaviors among patients with complicated Gram-negative bacterial infections (GNBI). We sought to characterize patient and treatment characteristics, details of regimen modification, and patient outcomes. Methods This retrospective chart review included patients, admitted from 1/1/2019-12/31/2020 to Hoag Memorial Hospital, with a complicated GNBI due to an extended spectrum cephalosporin resistant pathogen. We present an interim descriptive analysis of 60 patients: demographics, ABX modifications, rationale and timing for modifications, and patient outcomes. ABX modifications were defined a GNB ABX switched, added, or removed. Results The predominant culture sources were urine and bloodstream. ESBL organisms (38%) and Pseudomonas spp (32%) were most common. Inpatient initial empiric therapies included TZP (33%), MEM (20%), and CRO (17%). 32% of patients did not have any modifications to their ABX regimens. For patients where modifications occurred this ranged from 0 to 6 changes. Time to the first modification ranged from 2 – 196 hours. For initial modifications, all were considered escalations, and most were based on preliminary culture results (36%), lack of patient response (28%), additional history review (28%) and decompensation (1.7%). No difference in 30 or 90-day mortality or 90-day readmission was observed for patients that did or did not have ABX modifications. Conclusion Many patients experience modification to GNB targeted antibacterials, in almost all cases, rationale for change was documented. In this interim analysis no difference in patient outcomes was observed. However, it is well established that increased duration of therapy and exposure to numerous antibacterial agents can increase healthcare resource utilization and may negatively impact local ecology, respectively. Disclosures Jason Yamaki, PharmD, PhD, Merck & Co. Inc.,: Grant/Research Support Ryan J. Dillon, MSc, Merck: Employee|Merck: Stocks/Bonds.

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.

1182. Risk factors for colonization with extended-spectrum cephalosporin resistant and carbapenem resistant Enterobacterales among community adults, Bangladesh: An Antibiotic Resistance in Communities and Hospitals (ARCH) study

Abstract Background Antimicrobial resistant (AMR) organisms are an increasing global health threat that are spreading within communities. Understanding the risk factors for colonization with AMR organisms is critical for implementing prevention and control strategies, particularly in resource-limited settings such as Bangladesh. Methods During 2019, we conducted a population-based observational study in Dhaka (surveillance site of icddr,b). We collected stool samples from randomly selected adults and tested for Enterobacterales with extended-spectrum cephalosporin resistance (ESCrE) and carbapenem resistance (CRE) using selective media followed by VITEK-2 confirmation. Participants completed demographic surveys assessing food consumption, animal contact, sanitation, water sources, and healthcare exposure. We identified factors associated with ESCrE and CRE colonization using bivariable and multivariable logistic regression, adjusting for potential confounders and clustering. Results Of 714 enrolled individuals, 557 (78%) were colonized with ESCrE and 66 (9%) with CRE. In bivariable analysis, factors associated with ESCrE colonization included fresh fruit consumption in the past week (OR 1.8, 95% CI 1.2-2.9), public tap as main source of drinking water compared with basic improved source (OR 3.3, 1.0-11.0), and unimproved toilet (pour/flush to open drain, pit latrine without slab) compared with basic improved toilet (OR 11, 2.9-42.0). Only consumption of fresh fruit was significant in the multivariable analysis (aOR 2.0, 1.3-3.2). Factors associated with CRE colonization in bivariable analysis were hospitalization in the last 3 months (OR 3.2, 1.2-8.6), limited sanitation facility (improved toilet shared with other households) (OR 2.0, 1.0-3.8), and limited hygiene (availability of handwashing facility on premises without soap and/or water) (OR 3.3, 1.4-7.7). The only factor that was significant in multivariable analysis was hospitalization in the last 3 months (aOR 3.0, 1.0-8.7). Conclusion While ESCrE colonization is common in urban communities, hospitals may be contributing to community spread of CRE. Targeted interventions focused on healthcare facilities may be needed to mitigate the transmission of AMR organisms. 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.

Current Susceptibility Surveillance and Distribution of Antimicrobial Resistance in N. gonorrheae within WHO Regions.

Neisseria gonorrhoeae (N. gonorrhoeae) is the etiological agent of the second most common sexually transmitted disease in the world, gonorrhoea. Currently recommended and last available first-line therapy is extended-spectrum cephalosporins most often combined with azitromycin. However, misuse of antibiotics and the abilities of N. gonorrhoeae to acquire new genetic and plasmid-borne resistance determinants has gradually led to the situation where this bacterium has become resistant to all major classes of antibiotics. Together with a generally slow update of treatment guidelines globally, as well as with the high capacity of gonococci to develop and retain AMR, this may lead to the global worsening of gonococcal AMR. Since effective vaccines are unavailable, the management of gonorrhoea relies mostly on prevention and accurate diagnosis, together with antimicrobial treatment. The study overviews the latest results of mostly WHO-initiated studies, primarily focusing on the data regarding the molecular basis of the resistance to the current and novel most promising antibacterial agents, which could serve to establish or reinforce the continual, quality-assured and comparable AMR surveillance, including systematic monitoring and treatment with the use of molecular AMR prediction methods.

Treatment of Sexually Transmitted Infections (STIs) Caused by Neisseria gonorrhoeae and the Global Shortage of Antibiotics

The gonorrhoea caused by the bacterium Neisseria gonorrhoeae remains a major global public health problem with high morbidity. Gonorrhoea can affect both women and men, being more prevalent in sexually active young individuals. Even after infection from N. gonorrhoeae, many patients may remain asymptomatic, making the diagnosis and adequate treatment of the disease difficult. The treatment and control of gonorrhoea have been difficult in recent years in most populations, being an example of how behavioural, social, and demographic factors can influence the epidemiology of an infectious disease. The emergence of strains of N. gonorrhoeae resistant to multiple antimicrobials, especially to extended-spectrum cephalosporins, indicates that gonorrhoea has the potential to become untreatable in the current reality of treatment options, especially in places that have a high prevalence of gonococcal infections. The loss of available and effective treatment options can lead to significant increases in new cases of the disease, as well as increased morbidity and mortality. This review provides an overview of current therapeutic options for gonorrhoea, as well as ongoing experimental studies and clinical trials with new antigonococcal agents.

Detection of an IMI-2 carbapenemase-producing Enterobacter asburiae at a Swedish feed mill.

Occurrence of multidrug resistant Enterobacteriaceae in livestock is of concern as they can spread to humans. A potential introduction route for these bacteria to livestock could be animal feed. We therefore wanted to identify if Escherichia spp., Enterobacter spp., Klebsiella spp., or Raoutella spp. with transferable resistance to extended spectrum cephalosporins, carbapenems or colistin could be detected in the environment at feed mills in Sweden. A second aim was to compare detected isolates to previous described isolates from humans and animals in Sweden to establish relatedness which could indicate a potential transmission between sectors and feed mills as a source for antibiotic resistant bacteria. However, no isolates with transferable resistance to extended-cephalosporins or colistin could be identified, but one isolate belonging to the Enterobacter cloacae complex was shown to be carbapenem-resistant and showing carbapenemase-activity. Based on sequencing by both short-read Illumina and long-read Oxford Nanopore MinIon technologies it was shown that this isolate was an E. asburiae carrying a bla IMI-2 gene on a 216 Kbp plasmid, designated pSB89A/IMI-2, and contained the plasmid replicons IncFII, IncFIB, and a third replicon showing highest similarity to the IncFII(Yp). In addition, the plasmid contained genes for various functions such as plasmid segregation and stability, plasmid transfer and arsenical transport, but no additional antibiotic resistance genes. This isolate and the pSB89A/IMI-2 was compared to three human clinical isolates positive for bla IMI-2 available from the Swedish antibiotic monitoring program Swedres. It was shown that one of the human isolates carried a plasmid similar with regards to gene content to the pSB89A/IMI-2 except for the plasmid transfer system, but that the order of genes was different. The pSB89A/IMI-2 did however share the same transfer system as the bla IMI-2 carrying plasmids from the other two human isolates. The pSB89A/IMI-2 was also compared to previously published plasmids carrying bla IMI-2, but no identical plasmids could be identified. However, most shared part of the plasmid transfer system and DNA replication genes, and the bla IMI-2 gene was located next the transcription regulator imiR. The IS3-family insertion element downstream of imiR in the pSB89A was also related to the IS elements in other bla IMI-carrying plasmids.

Transfer of Extended Spectrum Cephalosporin Resistant Enterobacteriaceae Among Patients on an HSCT Unit and the Value of Surveillance and Contact Isolation

The mechanism(s) of acquisition of extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCRE) on inpatient hospital units dedicated to hematopoietic stem cell transplantation (HSCT) is unclear. The objectives of this study were to determine whether ESCRE organisms are transmitted among patients housed on a HSCT unit, clarify the mechanisms involved, and determine whether routine surveillance for ESCRE carriage and contact isolation for ESCRE carriers is beneficial. The study was conducted on a 30-bed inpatient unit dedicated to the care of patients with hematologic malignancies and HSCT recipients. To investigate whether ESCRE organisms may be transmitted vertically to subsequent room occupants, presumably through contamination of room surfaces, we (1) cultured 6 high touch areas in 10 rooms before and 9 rooms after terminal cleaning that had been occupied by patients with ESCRE carriage, (2) determined the in vitro survivals of our most common clinical ESCRE species, and (3) followed the subsequent room occupants of 54 consecutive ESCRE colonized patients for the development of inpatient acquired ESCRE carriage. To investigate whether ESCRE organisms are transmitted horizontally among inpatients we (1) sequenced 60 available ESCRE Escherichia coli isolates obtained from unit inpatients and searched for identities using complete-genome multisequence locus typing (cgMLST) and (2) retrospectively tabulated the cumulative rates of acquired ESCRE carriage in 356 patients admitted for a first HSCT before (200 patients) or after (156 patients) institution of universal ESCRE stool surveillance and contact isolation for carriers. No ESCRE organisms were cultured from patient rooms before or after terminal cleaning. In vitro, few, if any, ESCRE organisms survived longer than 2 hours. Nine of the subsequent occupants of a room in which a patient with ESCRE carriage had resided were detected with ESCRE carriage, only 2 of whom carried the same species as that of the prior occupant. DNA sequencing and cgMLST determination of the 60 E. coli isolates showed 53 cgMLST strains. Seven of the 53 strains were shared by 2 patients. After institution of universal ESCRE surveillance/isolation there was a significant decline in acquired ESCRE carriage among HSCT recipients. We conclude that vertical transmission of ESCRE organisms through room contamination appears to be uncommon on modern HSCT units. Conversely, our results are consistent with the horizontal spread of ESCRE organisms, probably mediated by intermediate vectors such as personnel or shared equipment. Further studies are needed to better define the magnitude of and risk factors for ESCRE horizontal transfers and the benefits of ESCRE surveillance/isolation.

Antibacterial spectrum of cefiderocol.

Cefiderocol, a siderophore catechol cephalosporin, recently introduced in the market has been developed to enhance the in vitro activity of extended spectrum cephalosporins and to avoid resistance mechanisms affecting cephalosporins and carbapenems. The in vitro study of cefiderocol in the laboratory requires iron depleted media when MIC values are determined by broth microdilution. Disk diffusion presents good correlation with MIC values. In surveillance studies and in clinical trials it has been demonstrated excellent activity against Gram-negatives, including carbapenemase producers and non-fermenters such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Few cefiderocol resistant isolates have been found in surveillance studies. Resistance mechanisms are not directly associated with porin deficiency and or efflux pumps. On the contrary, they are related with gene mutations affecting iron transporters, AmpC mutations in the omega loop and with certain beta-lactamases such us KPC-variants determining also ceftazidime-avibactam resistance, certain infrequent extended-spectrum betalactamases (PER, BEL) and metallo-beta-lactamases (certain NDM variants and SPM enzyme).

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection.

PurposeThis study aimed to identify the clinical outcomes, microbiological features and risk factors for difficult-to-treat resistance (DTR) Klebsiella pneumoniae (Kp) infection.Materials and MethodsA retrospective study was conducted at Peking University Third Hospital from January 2020 to March 2021. DTR was defined as resistance to ≥1 carbapenem, ≥1 extended-spectrum cephalosporin, and ≥1 fluoroquinolone. Hypervirulent Kp (HvKp) was defined as peg-344-, iroB-, iucA-, rmpA-, or rmpA2-positive. Clinical data were collected. Antimicrobial susceptibility testing and string tests were performed to determine resistance and hypermucoviscosity phenotype. Whole genome sequencing was performed to analyze the sequence type (ST), capsular serotypes, resistance and virulence genes. Risk factors for 30-day mortality were analyzed.ResultsFifty DTR-Kp (50.0%) strains were identified among 100 patients. Compared to non-DTR-Kp group, a significant number of patients with DTR-Kp infection experienced ICU admission (44.0% versus 10.0%, P<0.001) and mechanical ventilation after Kp detection (26.0% versus 10.0%, P=0.037). Notably, the percentage of hvKp among the DTR-Kp isolates increased consistently over the 15 months evaluated. Most DTR-Kp strains belonged to ST11 (82.0%), followed by ST15 (12.0%), ST86 (2.0%), ST996 (2.0%), and ST3157 (2.0%). DTR-Kp isolates possessed various resistance genes, such as blaKPC-2, blaTEM-1D and fosA3 (90.0%, 80.0% and 72.0%, respectively). Importantly, the yersiniabactin genes were significantly clustered in DTR group (48/50, 96.0%). The 30-day mortality was significantly higher in patients with DTR-Kp infection than non-DTR-Kp group (38.0% versus 8.2%, P=0.001). DTR-Kp infection (odds ratio [OR] = 4.196) was an independent risk factor for the 30-day mortality of Kp-infected patients. Additionally, cerebrovascular disease (OR = 2.780) and Charlson comorbidity index (OR= 1.584) were independent risk factors for DTR-Kp infections.ConclusionDTR-hvKp is rapidly emerging. The DTR-Kp strains harbored various resistance genes and high rates of yersiniabactin siderophore genes. DTR-Kp infection was an independent risk factor for mortality, suggesting that enhanced awareness essential.

Antimicrobial resistance trends among canine Escherichia coli isolated at a New York veterinary diagnostic laboratory between 2007 and 2020

Dogs are a potential source of drug-resistant Escherichia coli, but very few large-scale antimicrobial resistance surveillance studies have been conducted in the canine population. Here, we assess the antimicrobial susceptibility patterns, identify temporal resistance and minimum inhibitory concentration (MIC) trends, and describe associations between resistance phenotypes among canine clinical E. coli isolates in the northeastern United States. Through a retrospective study design, we collected MICs from 7709 E. coli isolates from canine infections at the Cornell University Animal Health Diagnostic Center between 2007 and 2020. The available clinical data were limited to body site. Isolates were classified as resistant or susceptible to six (urinary) and 22 (non-urinary) antimicrobials based on Clinical and Laboratory Standards Institute breakpoints. We used the Mann-Kendall test (MKT) and Sen's slope to identify the presence of a significant trend in the percent of resistant isolates over the study period. Multivariable logistic regression (MLR) models were built with ceftiofur, enrofloxacin, or trimethoprim-sulfamethoxazole resistance as the outcome and either body site and isolation date, or resistance to other antimicrobials as predictors. MIC trends were characterized with survival analysis models, controlling for body site and year of isolation. Overall, 16.4% of isolates were resistant to enrofloxacin, 14.3% to ceftiofur, and 14% to trimethoprim-sulfamethoxazole. The MKT and Sen's slope revealed a significant decreasing temporal trend for gentamicin and trimethoprim-sulfamethoxazole resistance among non-urinary isolates. No significant temporal resistance trends were detected by MKT for other antimicrobials. However, controlling for body-site in MLR models identified a decrease in resistance rates to enrofloxacin and trimethoprim-sulfamethoxazole after 2010. Similarly, survival analysis data confirmed these findings and showed a decrease in MIC values after 2010 for gentamicin and trimethoprim-sulfamethoxazole, but an increase in cephalosporin MICs. MLR showed that non-urinary isolates were significantly more likely than urinary isolates to demonstrate in vitro resistance to ceftiofur, enrofloxacin, and trimethoprim-sulfamethoxazole after controlling for year of isolation. We identified a higher level of ceftiofur resistance among enrofloxacin resistant isolates from urinary and non-urinary origins. Our findings confirmed that dogs are still a non-negligeable reservoir of drug-resistant E. coli in the northeastern United States. The increase in extended-spectrum cephalosporin MIC values in 2018–2020 compared to 2007–2010 constitutes a particularly worrying issue; the relationship between ceftiofur and enrofloxacin resistance suggests that the use of fluoroquinolones could contribute to this trend. Trimethoprim-sulfamethoxazole may be a good first-line choice for empiric treatment of E. coli infections; it is already recommended for canine urinary tract infections.

Characterization of extended-spectrum cephalosporins and fluoroquinolone resistance of a Salmonella enterica serovar Thompson isolate from ready-to-eat pork product in China.

Salmonella is a leading cause of foodborne illness worldwide and is a common concern in food safety. Salmonella enterica displaying resistance to extended-spectrum cephalosporins (ESCs) and fluoroquinolone (FQs) has been deemed a high-priority pathogen by the World Health Organization. Co-resistance to ESCs and FQs has been reported in S. enterica serovar Thompson (S. Thompson). However, the genetic context of ESCs and FQs resistance genes in S. Thompson lacks sufficient characterization. In this study, we characterized a multi-drug resistant (MDR) S. Thompson isolate recovered from a retail ready-to-eat (RTE) pork product in China. Short- and long-read sequencing (HiSeq and MinION) of the genome identified the presence of blaCMY−2, qnrS1, and qepA8, along with 11 additional acquired antimicrobial resistance genes, residing on a 152,940 bp IncA/C plasmid. Specifically, the blaCMY−2, qnrS1, and qepA8 genes were located in insertion sequences (ISs) and integron mediated mobile genetic structure, sugE-blc-blaCMY−2-ISEc9, IS26-orf6-qnrS1-orf5-ISKpn19, and intl1-qepA8-orf10-IS91-orf1-dfrA12-orf11-aadA2-qacEΔ1-sul1, respectively. Each gene was identified in various bacteria species, indicating their high transfer ability. The plasmid was found to be transferable to Escherichia coli J53 by conjugation and resulted in the acquiring of multiple resistances in the transconjugants. The plasmid is closely related to plasmids from two human S. Thompson strains isolated in different regions and years in China. Moreover, core-genome Multi Locus Sequence Typing (cgMLST) and phylogenetic analysis based on global 1,868 S. Saintpaul isolates showed that the S. Thompson isolate was highly epidemiologically linked to a human isolate in China. Our findings suggest that Chinese RTE pork products are a possible source of human pathogenic ESCs and FQs co-resistant S. Thompson. Furthermore, the results underline the important role of conjugative plasmids in acquiring and transmission of ESCs and FQs resistance in S. Thompson isolates, which need continuous investigation.

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States.

BackgroundManagement of pneumococcal disease is complicated by high rates of antimicrobial resistance (AMR). This study assessed AMR trends for Streptococcus pneumoniae isolates from adults with pneumococcal disease.MethodsFrom January 2011 to February 2020, we evaluated 30-day nonduplicate S. pneumoniae isolates from 290 US hospitals (BD Insights Research Database) from adults (≥18 years) in inpatient and outpatient settings. Isolates were required to have ≥1 AMR result for invasive (blood, cerebrospinal fluid/neurologic) or noninvasive (respiratory or ear/nose/throat) pneumococcal disease samples. Determination of AMR was based on facility reports of intermediate or resistant. Descriptive statistics and generalized estimated equations were used to assess variations over time.ResultsOver the study period, 34 039 S. pneumoniae isolates were analyzed (20 749 [61%] from noninvasive sources and 13 290 [39%] from invasive sources). Almost half (46.6%) of the isolates were resistant to ≥1 drug, and noninvasive isolates had higher rates of AMR than invasive isolates. Total S. pneumoniae isolates had high rates of resistance to macrolides (37.7%), penicillin (22.1%), and tetracyclines (16.1%). Multivariate modeling identified a significant increasing trend in resistance to macrolides (+1.8%/year; P < .001). Significant decreasing trends were observed for penicillin (−1.6%/year; P < .001), extended-spectrum cephalosporins (ESCs; −0.35%/year; P < .001), and ≥3 drugs (−0.5%/year; P < .001).ConclusionsDespite decreasing trends for penicillin, ESCs, and resistance to ≥3 drugs, AMR rates are persistently high in S. pneumoniae isolates among US adults. Increasing macrolide resistance suggests that efforts to address AMR in S. pneumoniae may require antimicrobial stewardship efforts and higher-valent pneumococcal conjugate vaccines.

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.

Enterobacterales high-risk clones and plasmids spreading blaESBL/AmpC and blaOXA-48 genes within and between hospitalized dogs and their environment.

Compared with healthcare settings, the role of veterinary hospitals in the spread of extended-spectrum cephalosporin- and carbapenem-resistant (ESC-R/CP-R) bacteria has been overlooked. To investigate using genome-based approaches the dynamics of ESC-R and CP-R Enterobacterales among 125 dogs admitted to the same veterinary hospital over a 4 month period. Dogs (n = 125) were sampled within 48 h of admission and at discharge. ESC-R/CP-R were phenotypically characterized and whole-genome sequenced using short- and long-read technologies. Phylogenetic analyses were performed using appropriate pipelines. ESC-R/CP-R prevalence in dogs was 4.8% (6/125) upon admission and reached 24.8% (31/125) at discharge, reflecting multiple acquisitions of ESBL/AmpC and OXA-48-positive Enterobacterales during hospitalization. Indistinguishable or closely related isolates were found within dogs, shared between dogs, and shared between dogs and their environment, suggesting numerous clonal and plasmid spreads. Even though carbapenems are not licensed for use in companion animals, a wide distribution of the blaOXA-48/IncL plasmid was evidenced across different bacterial species and dogs. This study highlights nosocomial acquisitions of ESBL/AmpC and carbapenemase-producing Enterobacterales by companion animals and the risk of further transmission within the community in a One Health perspective. Reinforced infection prevention and control measures and screening procedures are urgently needed in small animal veterinary settings where advanced therapeutics and intensive care is provided.