Extended-spectrum Cephalosporin-resistant Enterobacteriaceae Research Articles

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.

Extended spectrum cephalosporin resistant enterobacteriaceae carriage and infection in patients admitted with newly-diagnosed acute leukemia

Current information is limited on the incidence, risk factors, and consequences of extended-spectrum cephalosporin resistant Enterobacteriaceae (ESCRE) carriage in patients undergoing therapy for newly-diagnosed acute leukemia. We monitored 300 consecutive patients who submitted a first stool within the first week of initial hospitalization for initial and hospital acquired ESCRE carriage. Selected available isolates underwent DNA sequencing for determination of strain typing and resistance genes. 19 (6%) patients had ESCRE in their initial stool, and there was continued risk for new acquisition throughout their multiple hospitalizations. Patients with AML had more acquired carriage during their initial hospitalization. Increased hospitalizations and male sex were risk factors for detected acquired ESCRE carriage. ESCRE stool carriage was predictive for ESCRE BSI but not for overall survival. Sequencing revealed that E. coli ESCRE isolates contained primarily ESBL, while Enterobacter spp. and Citrobacter spp. showed primarily AmpC genes. The antibiotic sensitivity patterns for ESCRE BSI isolates reflected these genome findings. ESCRE carriage is common in patients with acute leukemia undergoing repeated hospitalizations and increases the risk for ESCRE BSI. ESCRE genera express differing resistance genes which may be predictive for empiric antibiotic efficacy.

Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods\xa0for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies

BackgroundAntimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area.MethodsResearchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study.DiscussionThis is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

The Implementation of Active Environmental Surveillance in a Veterinary Referral Hospital Setting

Emily Feyes, The Ohio State University College of Veterinary Medicine; Dixie Mollenkopf, The Ohio State University College of Veterinary Medicine; Thomas Wittum, The Ohio State University College of Veterinary Medicine; Dubraska Diaz-Campos, The Ohio State University College of Veterinary Medicine; Rikki Horne, The Ohio State University College of Veterinary MedicineBackground: The Ohio State University College of Veterinary Medicine (OSU-CVM) Antimicrobial Stewardship Working Group (ASWG) uses monthly environmental surveillance to understand the effectiveness of our veterinary medical center (VMC) infection control and biosecurity protocols in reducing environmental contamination with multidrug resistant organisms. Monthly surveillance allows us to monitor trends in the recovery of these resistant organisms and address issues of concern that could impact our patients, clients, staff, and students. Methods: The OSU-CVM ASWG collects samples from >100 surfaces within the companion animal, farm animal, and equine sections of our hospital each month. Sampling has been continuous since January 2018. Samples are collected from both human–animal contact and human-only contact surfaces using Swiffer electrostatic cloths. These samples are cultured for recovery of Salmonella spp, extended-spectrum cephalosporin-resistant Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae (CPE), and methicillin-resistant Staphylococcus spp. Results: The recovery of these antibiotic resistant target organisms is low in the environment of our hospital. Recovery from human-only contact surfaces (19.8%) is very similar to recovery from human–animal contact surfaces (25.5%). We commonly recover Enterobacteriaceae (E.coli, Klebsiella spp, and Enterobacter spp) that are resistant to extended-spectrum cephalosporins (496 of 2,016; 24.6%) from the VMC environment. These antibiotic-resistant indicator bacteria are expected in a veterinary hospital setting where use the of β-lactam drugs is common. Recovery of both Salmonella spp and CPE has remained very low in our hospital environment over the past 19 months: 16 of 2,016 (0.7%) for Salmonella and 15 of 2,016 (0.8%) for CPE. Discussion: The active environmental surveillance component of our antimicrobial stewardship program has allowed us to reduce the threat of nosocomial infections within our hospital and address environmental contamination issues before they become a problem. Our consistently low recovery of resistant organisms indicates the effectiveness of our existing cleaning and disinfection protocols and biosecurity measures. Due to the nature of our patient population, we do expect to find resistant organisms in the patient-contact areas of the hospital environment. However, our similar rates of resistant organisms from human-only surfaces (eg, computer keyboards, door handles, telephones, and Cubex machines) indicates a need to improve our hand hygiene practices. These data are now supporting the implementation of a new hand hygiene campaign in our veterinary hospital.Funding: NoneDisclosures: None

2657. Clinical Prediction Tool for Multidrug-Resistant Organisms Among Deceased Donors at the Time of Donor Evaluation

BackgroundTransplant guidelines recommend exercising caution when considering organs that may be infected or colonized with multidrug-resistant organisms (MDROs) and treating the organ recipient with perioperative antibiotics active against the donor MDRO. Unfortunately, donor MDROs are often identified only after transplantation. We developed a clinical prediction tool to stratify donors’ MDRO risk at the time of donor evaluation.MethodsA retrospective cohort study was conducted at four transplant centers in Philadelphia between January1, 2015 and June 30, 2016. All deceased organ donors who donated ≥1 organ to one of the centers were included. Multivariate logistic regression was used to determine predictors of donor MDROs, including methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci, extended-spectrum cephalosporin-resistant (ESC-R) or carbapenem-resistant Enterobacteriaceae, multidrug-resistant (MDR) P. aeruginosa, or MDR Acinetobacter species. Manual forward selection was utilized to maximize the area under the receiver operating characteristic curve (AUC). A scoring system was developed based on the odds ratios for each covariate. Internal validity was assessed using the Hosmer–Lemeshow statistic, specificity, and negative predictive value (NPV).ResultsOf 440 total donors, 62 (14%) grew MDROs on culture. The majority were MRSA (40) or ESC-R Enterobacteriaceae (20). The most parsimonious model that predicted donor MDROs included: a terminal hospitalization ≥ 7 days (1 point), ≥ 2 antibiotics administered during the terminal hospitalization (1 point), receipt of extracorporeal membrane oxygenation (ECMO) (1 point), and presence of opacities on donor chest imaging concerning for lower respiratory tract infection (2 points). With this scoring system, the maximum attainable score is 5; any donor with a score of ≥ 2 points would be considered high risk for an MDRO, with an AUC of 0.71, specificity of 99%, and NPV of 86%. The Hosmer–Lemeshow P = 0.68.ConclusionThe risk of an MDRO among deceased organ donors can be predicted using the above scoring system. This tool will inform decisions about organ utilization and perioperative prophylaxis for solid-organ transplant recipients. Disclosures All authors: No reported disclosures.

1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients

BackgroundDrug resistance in Gram-negative bacteria is of particular concern in children. Relebactam, a novel diazabicyclooctane inhibitor, coupled with imipenem has broad-spectrum activity against β-lactamase producing organisms. Here, we compare the in vitro activity of imipenem-relebactam to 10 standard comparator drugs against resistant Gram-negative isolates from two US pediatric hospitals.MethodsWe tested 100 isolates (50 per site) from pediatric clinical specimens tested during 2015–2017. All isolates were extended-spectrum cephalosporin-resistant (ESC-R); more than half were multidrug resistant (67%). Selected ESC-R isolates included Escherichia coli (90), Klebsiella pneumoniae (8), Klebsiella oxytoca (1), and Enterobacter cloacae (1) that were resistant or intermediate to ≥1 cephalosporins and/or aztreonam. A 0.5 McFarland suspension was prepared from colonies grown on blood agar plates (Thermo Scientific) at 35 ± 1°C for 18–24 hours. A final inoculum of 5 × 105 CFU/mL was prepared in Mueller–Hinton broth. Sensititre plates (Thermo Fisher Scientific) containing graded concentrations of imipenem/relebactam and 10 comparator drugs were inoculated and incubated at 35 ± 1°C for 18–24 hours. The minimum inhibitory concentration (MIC) was determined using the Sensititre Vizion system (Thermo Fisher Scientific) and endpoints were interpreted using CLSI (2019) breakpoint criteria, with the exception of colistin (EUCAST 2019).ResultsSelected ESC-R isolates had high rates of resistance to cephalosporins (64%–97%), aztreonam (80%), and levofloxacin (61%). All isolates were susceptible to imipenem/relebactam, imipenem and meropenem (MIC, ≤1 μg/mL for all). The imipenem/relebactam MIC50 (0.06 μg/mL) and MIC90 (0.12 μg/mL) values for ESC-R isolates were within one dilution of MICs of imipenem alone (0.12 μg/mL and 0.25 μg/mL). Among the comparators, colistin, amikacin, and piperacillin/tazobactam demonstrated comparable activities with 100%, 99%, and 94% susceptibilities, respectively.ConclusionMeropenem, imipenem alone and in combination with relebactam exhibited 100% susceptibilities against ESC-R Enterobacteriaceae isolated from pediatric specimens, demonstrating the high potency of carbapenems. Disclosures All authors: No reported disclosures.

Occurrence of and risk factors for extended-spectrum cephalosporin-resistant Enterobacteriaceae determined by sampling of all Norwegian broiler flocks during a six month period.

All broiler flocks reared and slaughtered in Norway from May-October 2016 (n = 2110) were screened for the presence of extended-spectrum cephalosporin (ESC) -resistant Enterobacteriaceae. Furthermore, we investigated possible risk factors for occurrence of such bacteria in broiler flocks. The odds of a flock being positive for ESC-resistant Enterobacteriaceae increased if the previous flock in the same house was positive, and if the flock was reared during September-October. However, we cannot exclude seasonal fluctuations in occurrence of ESC-resistant Enterobacteriaceae during the months November to April. The overall occurrence of ESC-resistant Enterobacteriaceae was 10.4%, and primarily linked to the presence of blaCMY (82.6%) in positive isolates. We describe the first findings of Escherichia coli with blaCTX-M-1, Klebsiella pneumoniae with both blaCTX-M-15 and blaSHV-12, and K. pneumoniae with blaCMY isolated from Norwegian broiler production. This study gives us a unique overview and estimate of the true occurrence of ESC-resistant Enterobacteriaceae in Norwegian broilers over a six-month period. To the best of our knowledge, this is the most comprehensive study performed on the occurrence of ESC-resistant Enterobacteriaceae in a broiler population.

Evaluation of essential oil obtained from Mentha×piperita L. against multidrug-resistant strains.

BackgroundBacterial multidrug resistance currently poses an increasingly serious threat, with important clinical consequences regarding treatment options. In 2017, the WHO released a global list of resistant bacteria, identifying multidrug-resistant (MDR) Gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter baumannii, extended-spectrum cephalosporin-resistant Enterobacteriaceae as critical priorities for developing new strategies of treatment.PurposeThe novelty presented in this study refers to the evaluation of the volatile oil obtained from the leaves of Mentha×piperita L., on MDR strains from hospitalized patients.Material and methodsThe essential oil was extracted by steam distillation and tested on six reference bacterial strains and also on the MDR strains collected from patients of the “Pius Brînzeu” Emergency Clinical County Hospital Timișoara. The in vitro antibacterial activity was evaluated by agar disk diffusion method and microdilution method.ResultsTesting the antibacterial activity of peppermint oil on both reference strains and isolated MDR strains from hospitalized patients demonstrated its bactericidal effect. Minimum inhibitory concentration (MIC) was lower (20 mg/mL) for Staphylococcus aureus, Escherichia coli and Proteus mirabilis and higher (40 mg/mL) for Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii strains. Minimum bactericidal concentration (MBC) was equal to MIC, with the exception of Pseudomonas aeruginosa strains, where MBC was the double of MIC.ConclusionThe present study highlights the bactericidal activity of Mentha×piperita L. essential oil on all tested MDR or extensively drug-resistant Gram-positive and Gram-negative strains of Staphylococcus aureus, Escherichia coli, Klebsiellapneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Acinetobacter baumannii. This oil may be a therapeutic option in the near future for many infectious diseases produced by MDR bacteria.

1168. Role of Extended-Spectrum Cephalosporin-Resistance in Recurrent Enterobacteriaceae Urinary Tract Infections

BackgroundRecent data have shown an increase in bacterial resistance to first-line antibiotics used to treat community-onset urinary tract infections (UTIs). A better understanding of the clinical outcomes associated with drug-resistant UTIs in the community is needed. We sought to determine the association between community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) UTI and the risk for recurrent UTI.MethodsA retrospective cohort study was performed. All patients presenting to the Emergency Departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable Cox proportional hazard regression analyses were performed to evaluate the association between ESC-R EB UTI and time to recurrent UTI within 12 months. Patients were censored at the time of first recurrent UTI or at the end of follow-up.ResultsA total of 302 patients with an index community-onset EB UTI were included, with 151 exposed and unexposed. Within 12 months of the index UTI, 163 (54%) patients experienced a recurrent UTI. The median time to recurrence was 69 days (interquartile range 25–183 days). On multivariable analyses, a UTI due to an ESC-R EB was associated with an increased hazard of recurrent UTI (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.01–1.91, P = 0.04). Other variables that were independently associated with an increased hazard of recurrent UTI included a history of UTI in the 6 months prior to the index UTI (HR 1.59, 95% CI 1.17–2.15, P < 0.01) and presence of a urinary catheter at the time of the index UTI diagnosis (HR 1.59, 95% CI 1.06–2.38, P = 0.03).ConclusionCommunity-onset UTI due to an ESC-R EB organism is associated with a significantly increased hazard of recurrent UTI within 12 months even after adjusting for baseline factors that predispose patients to UTI recurrence. This study raises the question of whether patients with an ESC-R EB organism may require modified treatment regimens. Further study is needed to better elucidate the cause of recurrence among these patients.Disclosures All authors: No reported disclosures.

Poor clinical outcomes associated with community-onset urinary tract infections due to extended-spectrum cephalosporin-resistant Enterobacteriaceae.

Resistance to extended-spectrum cephalosporins (ESC) among Enterobacteriaceae (EB) is increasingly prevalent. We sought to determine the clinical outcomes associated with community-onset ESC-resistant (ESC-R) EB urinary tract infections (UTIs) in a US health system. Retrospective cohort study.PatientsAll patients presenting to the emergency departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and the outcomes of clinical failure and inappropriate initial antibiotic therapy (IIAT). A total of 302 patients with community-onset EB UTI were included, with 151 exposed and unexposed. On multivariable analyses, UTI due to an ESC-R EB was significantly associated with clinical failure (odds ratio [OR], 7.07; 95% confidence interval [CI], 3.16-15.82; P<.01). Other independent risk factors for clinical failure included infection with Citrobacter spp and need for hemodialysis. UTI due to an ESC-R EB was also significantly associated with IIAT (OR, 4.40; 95% CI, 2.64-7.33; P<.01). Community-onset UTI due to an ESC-R EB organism is significantly associated with clinical failure, which may be due in part to IIAT. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt diagnosis and appropriate antibiotic prescribing for ESC-R EB.

Gut microbiota dynamics in travelers returning from India colonized with extended-spectrum cephalosporin-resistant Enterobacteriaceae: A longitudinal study.

Intestinal colonization by extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESC-R-Ent) has been attributed to travel to high prevalence countries. However, the dynamics of the microbiota changes during ESC-R-Ent colonization and whether there is a particular bacterial composition which is associated with subsequent colonization is unknown. Forty healthy volunteers living in Switzerland underwent screening before and after a trip to India, and also 3, 6 and 12 months after traveling. Culture-based ESC-R-Ent screening and microbiota analysis based on 16S rRNA amplicon sequencing were performed at all time points. Prevalence of ESC-R-Ent colonization before traveling was 10% (n = 4), whereas it increased to 76% (n = 31) after the trip. Based on bacterial diversity analyses of the gut microbiota, there were few but significant differences for colonized versus non-colonized individuals. However, an alternative, cluster based analysis revealed that individuals remained in the same cluster over time indicating that neither traveling nor ESC-R-Ent colonization significantly influences bacterial composition. Moreover, none of the found microbiota clusters were significantly associated with subsequent risk of ESC-R-Ent colonization. Based on their microbiota patterns, every volunteer was at the same risk of ESC-R-Ent colonization while traveling to India. Therefore, other risk factors for ESC-R-Ent colonization are responsible for this phenomenon.

Prevalence and molecular features of ESBL/pAmpC-producing Enterobacteriaceae in healthy and diseased companion animals in Brazil

Extended-spectrum beta-lactamase (ESBL)- and plasmid-mediated AmpC (pAmpC)-carrying Enterobacteriaceae have widely disseminated in human, animal and environmental reservoirs. Pets have been recognized as a source of ESBL/pAmpC worldwide, and are possibly also a source of human contamination. The aim of this study was to document to what extent cats and dogs may act as a driving force in the spread of ESBLs and pAmpCs in Brazil. A total of 113 healthy stray cats and dogs and 74 sick pets were sampled, and extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESC-R) were detected in 28/113 (24.8%) and 8/74 (10.8%) tested animals, respectively. Different Enterobacteriaceae isolates (mostly E. coli), a large number of E. coli clones (with ST90, ST457, ST973 and ST2541 being predominant), and several ESBL/pAmpC genes and plasmids were characterized, highlighting the ability of stray and pet cats and dogs to further spread a wide range of ESC-resistance determinants. The ESBL phenotype was due to the blaCTX-M-2 and blaCTX-M-8 genes, as found in human epidemiology in Brazil, but blaCTX-M-9 and blaCTX-M-15 were also identified. The pAmpC phenotype was systematically due to the presence of the blaCMY-2 gene, mostly carried by IncI1 ST12 plasmids. Our results showed that pets can be considered a significant reservoir of multidrug-resistant bacteria in Brazil. This is especially true for healthy stray dogs that displayed the highest prevalence (24.8%) of ESBLs/pAmpC resistance determinants, which can then be further spread both to the environment and to other animals or humans by contact.

Occurrence and characterization of extended-spectrum cephalosporin-resistant Enterobacteriaceae in healthy household dogs in Greece.

Extended-spectrum cephalosporin- and/or carbapenem-resistant (ESCR and/or CarbR) Enterobacteriaceae constitute a public health hazard because of limited treatment options and are endemic among humans in Greece. Recently, ESCR and CarbREnterobacteriaceae have been increasingly isolated from companion animals, stressing their potential role as a reservoir for humans. However, the presence of ESCR bacteria in companion animals within Greek households has not been determined yet. Genes conferring the ESCR and CarbR phenotype were detected among canine isolates and their chromosomal or plasmid location was determined. Standard methods were applied for plasmid characterization. The clonal relatedness of the recovered isolates was examined by multilocus sequence typing (MLST). Here, we report the first findings on the presence of ESCREnterobacteriaceae in healthy Greek dogs. ESCREscherichia coli isolates were associated with different sequence types (STs), including the human pandemic ST131 clone. The occurrence of human-related ESBL/pAmpC genes, plasmid types and/or strain STS in this animal reservoir suggests possible bilateral transmission.

High Prevalence of Intra-Familial Co-colonization by Extended-Spectrum Cephalosporin Resistant Enterobacteriaceae in Preschool Children and Their Parents in Dutch Households.

Extended-spectrum cephalosporin-resistant (ESCR) Enterobacteriaceae pose a serious infection control challenge for public health. The emergence of the ESCR phenotype is mostly facilitated by plasmid-mediated horizontal extended-spectrum β-lactamases (ESBLs) and AmpC gene transfer within Enterobacteriaceae. Current data regarding the plasmid contribution to this emergence within the Dutch human population is limited. Hence, the aim of this study was to gain insight into the role of plasmids in the dissemination of ESBL/AmpC genes inside Dutch households with preschool children and precisely delineate co-colonization. In 87 ESCR Enterobacteriaceae from fecal samples of parents and preschool children within 66 Dutch households, genomic localization, plasmid type and insertion sequences linked to ESBL/AmpC genes were determined. Chromosomal location of ESBL/AmpC genes was confirmed when needed. An epidemiologically relevant subset of the isolates based on household co-carriage was assessed by Multilocus Sequence Typing and Pulsed-Field Gel Electrophoresis for genetic relatedness. The narrow-host range I1α and F plasmids were the major facilitators of ESBL/AmpC-gene dissemination. Interestingly, we documented a relatively high occurrence of chromosomal integration of typically plasmid-encoded ESBL/AmpC-genes. A high diversity of non-epidemic Escherichia coli sequence types (STs) was revealed; the predominant STs belonged to the pandemic lineages of extraintestinal pathogenic E. coli ST131 and ST69. Intra-familiar co-carriage by identical ESCR Enterobacteriaceae was documented in 7 households compared to 14 based on sole gene typing, as previously reported. Co-carriage was more frequent than expected based on pure chance, suggesting clonal transmission between children and parents within the household.

Poor Clinical Outcomes Associated with Community-Onset Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae Urinary Tract Infections

BackgroundUrinary tract infections (UTIs) are the most common bacterial infection among adults in the community. Recent data suggest an increase in bacterial resistance to first line antibiotics used for UTI, though the impact on clinical outcomes is unclear. The objective of our study was to determine clinical outcomes associated with community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) UTI.MethodsA retrospective cohort study was conducted in a large health system from 2010 to 2013. All patients presenting to an emergency department or outpatient clinic with UTI due to EB were included. Exposed subjects were those with an EB demonstrating resistance to an ESC (ceftriaxone or ceftazidime). Unexposed subjects were those with ESC-susceptible EB UTIs and were matched to cases 1:1 based on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and 1) clinical failure (defined as ongoing symptoms, repeat positive culture, or need for additional antibiotics within 7 days); 2) inappropriate initial antibiotic therapy (IIAT) (defined as failure to receive an antibiotic to which the organism was susceptible within 48 hours of presentation).ResultsA total of 302 patients with community-onset EB UTI were included. On multivariable analyses, a UTI with an ESC-R EB was significantly associated with clinical failure (odds ratio [OR] 5.12, 95% confidence interval [CI] 2.79–9.39, P < 0.01). Other variables independently associated with clinical failure included presence of pyelonephritis at the time of UTI diagnosis (OR 2.15, 95% CI 1.14–4.03, p 0.02) and infection with Citrobacter species (OR 29.56, 95% CI 4.46–195.91, P < 0.01). ESC-R EB UTI was also associated with IIAT on multivariable analysis (OR 3.73, 95% CI 2.25–6.21, P < 0.01).ConclusionCommunity-onset UTI due to an ESC-R EB organism is associated with a significantly increased risk of clinical failure, which may be due in part to the use of inappropriate initial antibiotic therapy. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt urine culture ordering and appropriate antibiotic prescribing for ESC-R EB.Disclosures All authors: No reported disclosures.

The Molecular and Clinical Epidemiology of Extended-Spectrum Cephalosporin- and Carbapenem-Resistant Enterobacteriaceae at 4 US Pediatric Hospitals.

In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged <22 years from 4 freestanding pediatric medical centers were collected along with the associated clinical data. The overall frequencies of ESC-R and CR isolates according to hospital over the 4-year study period ranged from 0.7% to 2.8%. Rates of ESC-R or CR Escherichia coli and Klebsiella pneumoniae varied according to hospital and ranged from 0.75 to 3.41 resistant isolates per 100 isolates (P < .001 for any differences). E coli accounted for 272 (77%) of the resistant isolates; however, a higher rate of resistance was observed in K pneumoniae isolates (1.78 vs 1.27 resistant isolates per 100 same-species isolates, respectively; P = .005). One-third of the infections caused by ESC-R or CR E coli were community-associated. In contrast, infections caused by ESC-R or CR K pneumoniae were more likely than those caused by resistant E coli to be healthcare- or hospital-associated and to occur in patients with an indwelling device (P ≤ .003 for any differences, multivariable logistic regression). Nonsusceptibility to 3 common non-β-lactam agents (ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole) occurred in 23% of the ESC-R isolates. The sequence type 131-associated fumC/fimH-type 40-30 was the most prevalent sequence type among all resistant E coli isolates (30%), and the clonal group 258-associated allele tonB79 was the most prevalent allele among all resistant K pneumoniae isolates (10%). The epidemiology of ESC-R and CR Enterobacteriaceae varied according to hospital and species (E coli vs K pneumoniae). Both community and hospital settings should be considered in future research addressing pediatric ESC-R Enterobacteriaceae infection.

Clinical and Molecular Characterization of Community-Onset Urinary Tract Infections Due to Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae.

OBJECTIVE To evaluate risk factors for and molecular characteristics of community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) urinary tract infections (UTIs) in a US health system. DESIGN Case-control study. PARTICIPANTS All patients presenting to the emergency department or outpatient practices with EB UTIs from December 21, 2010, through April 22, 2013, were included. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched 1:1 on study year. METHODS Risk factors for ESC-R EB UTI were assessed using multivariable conditional logistic regression. A subset of case isolates was evaluated for extended-spectrum beta-lactamases. RESULTS A total of 302 patients with community-onset EB UTI were included, of which 151 were cases. On multivariable analysis, risk factors for ESC-R EB UTI included trimethoprim-sulfamethoxazole use in the prior 6 months (odds ratio, 2.40 [95% CI, 1.22-4.70]; P=.01), older age (1.03 [1.01-1.04]; P<.001), diabetes (2.91 [1.32-6.41]; P=.008), and presentation to the emergency department ( 2.42 [1.31-4.46]; P=.005). The prevalence of extended-spectrum beta-lactamases among 120 case isolates was 52% CTX-M, 29% TEM, 20% OXA, and 13% SHV. The prevalence of AmpC was 25%. Pulsed-field gel electrophoresis of the CTX-M Escherichia coli isolates showed no distinct clusters. CONCLUSIONS Use of trimethoprim-sulfamethoxazole, older age, diabetes, and presentation to the emergency department were associated with community-onset ESC-R EB UTI. There was a high prevalence of CTX-M among our community isolates. Further studies are needed to determine strategies to limit emergence of these organisms in the community. Infect Control Hosp Epidemiol 2016;1433-1439.

Polyclonal Intestinal Colonization with Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae upon Traveling to India.

We aimed to assess the intestinal colonization dynamics by multiple extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESC-R-Ent) clones in Swiss travelers to India, a country with high prevalence of these multidrug-resistant pathogens. Fifteen healthy volunteers (HVs) colonized with ESC-R-Ent after traveling to India who provided stools before, after, and at 3- and 6-month follow-up are presented in this study. Stools were enriched in a LB broth containing 3 mg/L cefuroxime and plated in standard selective media (BLSE, ChromID ESBL, Supercarba) to detect carbapenem- and/or ESC-R-Ent. At least 5 Enterobacteriaceae colonies were analyzed for each stool provided. All strains underwent phenotypic tests (MICs in microdilution) and molecular typing to define bla genes (microarray, PCR/sequencing), clonality (MLST, rep-PCR), and plasmid content. While only three HVs were colonized before the trip, all participants had positive stools after returning, but the colonization rate decreased during the follow-up period (i.e., six HVs were still colonized at both 3 and 6 months). More importantly, polyclonal acquisition (median of 2 clones, range 1–5) was identified at return in all HVs. The majority of the Escherichia coli isolates belonged to phylogenetic groups A and B1 and to high diverse non-epidemic sequence types (STs); however, 15% of them belonged to clonal complex 10 and mainly possessed blaCTX−M−15 genes. F family plasmids were constantly found (~80%) in the recovered ESC-R-Ent. Our results indicate a possible polyclonal acquisition of the ESC-R-Ent via food-chain and/or through an environmental exposure. For some HVs, prolonged colonization in the follow-up period was observed due to clonal persistence or presence of the same plasmid replicon types in a new bacterial host. Travel medicine practitioners, clinicians, and clinical microbiologists who are facing the returning travelers and their samples for different reasons should be aware of this important phenomenon, so that better infection control measures, treatment strategies, and diagnostic tests can be adopted.

423Comparison of pediatric community-acquired, healthcare-associated, and hospital-acquired infections caused by extended-spectrum cephalosporin-resistant Enterobacteriaceae

423Comparison of pediatric community-acquired, healthcare-associated, and hospital-acquired infections caused by extended-spectrum cephalosporin-resistant Enterobacteriaceae

Characteristics of Extended-Spectrum Cephalosporin-Resistant Escherichia coli Isolated from Swiss and Imported Poultry Meat

A worrisome phenomenon is the progressive global spread of Enterobacteriaceae in poultry and chicken meat expressing plasmid-mediated enzymes that inactivate β-lactam antibiotics, suggesting that the food chain might play a role in the epidemiology and the transmission of extended-spectrum cephalosporin-resistant Enterobacteriaceae to humans. The aim of the present study was to further characterize 24 extended-spectrum cephalosporin-resistant Enterobacteriaceae isolated from domestic and imported poultry meat by antibiotic susceptibility testing, identification of the blaESBL/blapAmpC genes, conjugation mating experiments and determination of plasmid incompatibility types, multilocus sequence typing, and analysis of the Escherichia coli phylogenetic groups. On account of their resistance patterns, 21 of the total 24 isolates were classified as multidrug resistant. Eleven isolates carried a blaCMY-2 gene, whereas 13 isolates harbored a blaCTX-M-1 gene. All isolates harbored plasmids that were assigned to 8 of the 18 described plasmid incompatibility groups, the most frequent of which were IncI1, IncFIB, IncB/O, and IncFrepB. The blaESBL/blapAmpC genes were harbored mainly by transferable IncI1 and IncB/O plasmids. Multilocus sequence typing as well as E. coli phylogenetic group typing revealed a high heterogenicity even among different isolates of the same sample.