Susceptible Enterobacteriaceae Research Articles

An investigation of the presence and antimicrobial susceptibility of Enterobacteriaceae in raw and cooked kibble diets for dogs in the United Kingdom.

Raw meat diets (RMD) for dogs are an increasingly popular alternative pet food choice, however studies worldwide have demonstrated them to be contaminated with zoonotic and antimicrobial resistant (AMR) bacteria, including bacteria resistant to critically important antibiotics. Despite this, few data exist surrounding the presence of these bacteria in RMD in the United Kingdom. The present study aimed to identify the most commonly selected RMD and non-raw diets (NRMD) by United Kingdom dog owners. Additionally, it investigated the presence of AMR-Enterobacteriaceae in samples of pre-prepared RMD and cooked commercial kibble dog foods. An online survey investigating diet preferences of United Kingdom dog owners was open for 6 weeks between February-March 2020. From this, the top 10 brands of pre-prepared raw and cooked kibble diets were ascertained and 134 samples purchased (110 RMD, 24 kibble) and subjected to microbiological testing. Bacterial enumeration of E. coli and other Enterobacteriaceae was undertaken, and the presence of Salmonella spp. and AMR-E. coli within samples determined. Whole genome sequencing was undertaken on Salmonella spp. and third-generation cephalosporin-resistant 3GCR-E. coli isolates. Pre-prepared RMD was most commonly selected by dog owners who fed RMD, and cooked commercial complete dry food was most frequently fed by owners who fed NRMD. Damaged and leaking packaging was observed in samples of RMD, alongside variability in information provided surrounding product traceability. Counts of E. coli and other Enterobacteriaceae exceeding >5,000 CFU/g were identified in samples of RMD. AMR-, extended-spectrum beta-lactamase (ESBL)-producing and 3GCR-E. coli was isolated from 39, 14 and 16% of RMD samples, respectively. Multiple antimicrobial resistance genes were identified in 3GCR-E. coli isolates. Of the ESBL encoding genes, blaCTX-M-15 was most commonly identified. S. enterica was isolated from 5% of RMD samples. No Enterobacteriaceae were isolated from any of the cooked kibble samples. The present study suggests that pre-prepared RMD available for dogs in the United Kingdom can be contaminated with zoonotic and AMR-Enterobacteriaceae. RMDs, therefore, are potentially an important One Health concern. Veterinary and medical professionals, pet food retailers and pet owners should be aware of these risks; and stringent hygiene measures should be practiced if owners choose to feed RMD.

2250. Fluoroquinolone Stewardship at a Veterans Affairs Facility: A Six Year Review

Abstract Background Increased utilization of antibiotics leads to decreased antimicrobial susceptibility, a well-established phenomenon. Antimicrobial stewardship programs (ASP) promote appropriate prescribing of antibiotics by decreasing inappropriate use, aiming to improve patient outcomes and reducing antimicrobial resistance. Fluroquinolones (FQ) are among the most prescribed antibiotics. We describe out institutional FQ use since inception of our ASP and followed the trend for susceptibility of Enterobacteriaceae and Pseudomonas Methods Northport Veterans Affairs Medical Center (VAMC) provides care for over 30000 Veterans in Long Island, New York, with emergency room, acute care hospital, nursing homes and outpatient clinics A Retrospective review investigated FQ use by total refills per year and by days of therapy per 1000 patient days at Northport VAMC from 2012 to 2022, along with review of local annual antibiograms focusing on ciprofloxacin susceptibility to E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa. An ASP in our facility was initiated in 2016. FQs are restricted antibiotics and require approval by the infectious diseases team (attendings, fellows, pharmacist) Results Figure 1 provides the outpatient total fills per year for Ciprofloxacin, Levofloxacin, Moxifloxacin. Inpatient FQ use during the ASP years was low: Figure 2 shows the FQ inpatient use (days of therapy/1000days) from 2019 to 2022. Comparing years 2012-2016 vs 2017-2022 there was a decrease in fills of ciprofloxacin (median 604 vs. 308 fills, P: 0.009), levofloxacin (276 vs. 116, P: 0.032), and moxifloxacin (116 vs. 14, P: 0.015). By same period comparison (see figure 3), Ciprofloxacin susceptibility for E. coli ranged median 66.5% to 61.5%, P: 0.126, K. pneumoniae 67% vs. 75.5% P: 0.086, P. mirabilis 45% vs. 47.5% P: 0.451, and P. aeruginosa 63% vs. 68.5% P: 0.308 Figure 2 inpatient FQ use 2019 to 2022 Figure 3 Ciprofloxacin susceptibility trend over time Conclusion There was a statistically significant decrease in the use of FQ in the outpatient setting after ASP was initiated in our facility. Although there was a trend in improvement in ciprofloxacin susceptibilities for Klebsiella, Proteus, and Pseudomonas, it was not statistically significant. Nevertheless, our results show that reducing FQ consumption can prevent worsening susceptibility trends for enteric gram negatives and Pseudomonas. Disclosures All Authors: No reported disclosures

Stability of temocillin in outpatient parenteral antimicrobial therapy: is it a real option?

Temocillin is an interesting alternative to carbapenems for susceptible Enterobacteriaceae. Although its use in outpatient parenteral antimicrobial therapy (OPAT) programmes has generated interest, this has been hampered by the lack of stability data. The purpose of the present study was to evaluate the physical and chemical stability of temocillin at the recommended dose for its use in OPAT programmes, contained in polypropylene infusion bags or polyisoprene elastomeric devices at different temperatures, and to describe a novel LC-MS/MS developed for the quantification of temocillin. Temocillin daily dose (6 g) was diluted in 500 mL of 0.9% sodium chloride to obtain a final concentration of 12 g/L. This solution was stored at 4°C, 25°C, 32°C and 37°C for 72 h, both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated during 72 h after manufacturing. Solutions were considered stable if colour, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%. Temocillin attained the chemical stability criterion of ≥90% of the original concentration for the whole experiment in both devices at 4°C, 25°C and 32°C. At 37°C, temocillin was stable for 24 h but its concentration dropped below 90% from that timepoint. No precipitation occurred and minor colour changes were observed. Temocillin is stable under OPAT conditions and it would be an appropriate candidate for the treatment of patients who can be discharged to complete therapy in an OPAT programme. For this study, an LC-MS/MS method was developed.

Retrospective Analysis of Sensitivity Characteristics of Enterobacteriaceae: A Study Based on Specimen Types, Sex, and Age Bracket of Patients.

Enterobacteriaceae have displayed widespread trends of antimicrobial resistance in recent years. Therefore, we aimed to analyse the antimicrobial susceptibility of common bacteria and explore the significance in treatment and research of infections induced by Enterobacteriaceae. We retrospectively analysed 10,775 antimicrobial susceptibility test results acquired over a 6-year period in the affiliated hospital of Chengde Medical University. We divided the data based on specimen type (blood, sputum, pus, or urine), and population characteristics (age bracket and sex) for analysis. We mainly analysed the antimicrobial susceptibility of Escherichia coli (Eco), Klebsiella pneumoniae (Kpn), and Enterobacter cloacae (Ecl). In our study, it was found that the resistance rates of Eco, Kpn, and Ecl to most antimicrobial agents were significantly different (P < 0.05) on specimen type and age bracket. The Eco from sputum had the highest resistance rates except ciprofloxacin (CIP), levofloxacin (LVX), and gentamicin (GEN); the Kpn from urine had the highest resistance rates to all antimicrobial agents; the Ecl from urine had the highest resistance rates to most antimicrobial agents. The Eco from geriatric patients had the highest resistance rates except GEN and SXT; the Kpn from adult patients had the lowest resistance rates to most antimicrobial agents except LVX. The Eco isolated from males had higher resistance rates to most antimicrobial agents except CIP, LVX, and NIT than those isolated from females; the Kpn showed significant differences in antimicrobial susceptibility to only 5 out of 22 antimicrobial agents (P < 0.05); the Ecl showed significant differences in susceptibility only to two antimicrobial agents, LVX and TOB (P < 0.01). The antimicrobial susceptibility of Enterobacteriaceae was significantly different among specimen type, age bracket and sex of patients, which is of great significance for the treatment and research of infection.

Lineages, Virulence Gene Associated and Integrons among Extended Spectrum β-Lactamase (ESBL) and CMY-2 Producing Enterobacteriaceae from Bovine Mastitis, in Tunisia.

Extended Spectrum Beta-Lactamase (ESBL) Enterobacteriaceae are becoming widespread enzymes in food-producing animals worldwide. Escherichia coli and Klebseilla pneumoniae are two of the most significant pathogens causing mastitis. Our study focused on the characterization of the genetic support of ESBL/pAmpC and antibiotic resistance mechanisms in cefotaxime-resistant (CTXR) and susceptible (CTXS) Enterobacteriaceae isolates, recovered from bovine mastitis in Tunisia, as well as the analyses of their clonal lineage and virulence-associated genes. The study was carried out on 17 ESBL/pAmpC E. coli and K. pneumoniae and 50 CTXS E. coli. Detection of resistance genes and clonal diversity was performed by PCR amplification and sequencing. The following β-lactamase genes were detected: blaCTX-M-15 (n = 6), blaCTX-M-15 + blaOXA-1 (2), bla CTX-M-15 + blaOXA-1 + blaTEM-1b (2), blaCTX-M-15 + blaTEM-1b (4), blaCMY-2 (3). The MLST showed the following STs: ST405 (n = 4 strains); ST58 (n = 3); ST155 (n = 3); ST471 (n = 2); and ST101 (n = 2). ST399 (n = 1) and ST617 (n = 1) were identified in p(AmpC) E. coli producer strains. The phylogroups A and B1 were the most detected ones, followed by the pathogenic phylogroup B2 that harbored the shigatoxin genes stx1/stx2, associated with the cnf, fimA, and aer virulence factors. The qnrA/qnrB, aac(6′)-Ib-cr genes and integrons class 1 with different gene cassettes were detected amongst these CTXR/S isolated strains. The presence of different genetic lineages, associated with resistance and virulence genes in pathogenic bacteria in dairy farms, may complicate antibiotic therapies and pose a potential risk to public health.

Clinical, epidemiological and microbiological characterization of bacteremia produced by carbapenem-resistant enterobacteria in a university hospital in Córdoba, Argentina

Enterobacteriaceae are a major cause of bloodstream infections and their antimicrobial resistance continues to increase. This leads to higher morbidity-mortality rates and public health costs. Carbapenem-resistant Enterobacteriaceae represent a serious challenge globally, since there are few therapeutic options available. Clinical/microbiological characterization of the carbapenem-resistant bacteremia observed over a period of 4 years. Retrospective, observational and descriptive study about bacteremia caused by carbapenem-resistant and susceptible Enterobacteriaceae. A total of 84 patients with bacteremia including carbapenem-resistant and susceptible Enterobacteriaceae were analyzed. We found that patients infected with carbapenem-resistant strains presented a higher proportion of: previous antibiotic treatment, hospitalization in intensive care unit (ICU), onset of the bacteremia during hospitalization in ICU and previous infection with extended-spectrum-beta-lactamase producing Enterobacteriaceae. Additionally, we observed a predominance of KPC-producing Klebsiella pneumoniae and an attributable mortality rate of 52.4%. This study allowed for a better understanding of an emerging problem with high mortality, which in turn is useful for the design and adoption of infection control strategies and effective treatment regimens adapted to our local epidemiology.

An Intertwined Network of Regulation Controls Membrane Permeability Including Drug Influx and Efflux in Enterobacteriaceae.

The transport of small molecules across membranes is a pivotal step for controlling the drug concentration into the bacterial cell and it efficiently contributes to the antibiotic susceptibility in Enterobacteriaceae. Two types of membrane transports, passive and active, usually represented by porins and efflux pumps, are involved in this process. Importantly, the expression of these transporters and channels are modulated by an armamentarium of tangled regulatory systems. Among them, Helix-turn-Helix (HTH) family regulators (including the AraC/XylS family) and the two-component systems (TCS) play a key role in bacterial adaptation to environmental stresses and can manage a decrease of porin expression associated with an increase of efflux transporters expression. In the present review, we highlight some recent genetic and functional studies that have substantially contributed to our better understanding of the sophisticated mechanisms controlling the transport of small solutes (antibiotics) across the membrane of Enterobacteriaceae. This information is discussed, taking into account the worrying context of clinical antibiotic resistance and fitness of bacterial pathogens. The localization and relevance of mutations identified in the respective regulation cascades in clinical resistant strains are discussed. The possible way to bypass the membrane/transport barriers is described in the perspective of developing new therapeutic targets to combat bacterial resistance.

Increased Azithromycin Susceptibility of Multidrug-Resistant Gram-Negative Bacteria on RPMI-1640 Agar Assessed by Disk Diffusion Testing.

Increasing antibiotic resistances and a lack of new antibiotics render the treatment of Gram-negative bacterial infections increasingly difficult. Therefore, additional approaches are being investigated. Macrolides are not routinely used against Gram-negative bacteria due to lack of evidence of in vitro effectiveness. However, it has been shown that Pseudomonas spp. are susceptible to macrolides in liquid RPMI-1640 and clinical data suggest improvement in patients’ outcomes. So far, these findings have been hardly applicable to the clinical setting due to lack of routine low-complexity antimicrobial susceptibility testing (AST) for macrolides. We therefore optimized and compared broth microdilution and disk diffusion AST. Multidrug-resistant Gram-negative bacteria (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa) were tested for azithromycin susceptibility by disk diffusion and broth microdilution in Mueller–Hinton and RPMI-1640 media. Azithromycin susceptibility of Enterobacteriaceae and a subgroup of P. aeruginosa increased significantly on RPMI-1640 agar compared to Mueller–Hinton agar. Further, a significant correlation (Kendall, τ, p) of zone diameters and minimal inhibitory concentrations (MICs) was found on RPMI-1640 agar for E. coli (−0.4279, 0.0051), E. cloacae (−0.3783, 0.0237) and P. aeruginosa (−0.6477, <0.0001). Performing routine disk diffusion AST on RPMI-1640 agar may lead to the identification of additional therapeutic possibilities for multidrug-resistant bacterial infections in the routine clinical diagnostic setting.

Differential DNA accessibility to polymerase enables 30-minute phenotypic β-lactam antibiotic susceptibility testing of carbapenem-resistant Enterobacteriaceae.

The rise in carbapenem-resistant Enterobacteriaceae (CRE) infections has created a global health emergency, underlining the critical need to develop faster diagnostics to treat swiftly and correctly. Although rapid pathogen-identification (ID) tests are being developed, gold-standard antibiotic susceptibility testing (AST) remains unacceptably slow (1–2 d), and innovative approaches for rapid phenotypic ASTs for CREs are urgently needed. Motivated by this need, in this manuscript we tested the hypothesis that upon treatment with β-lactam antibiotics, susceptible Enterobacteriaceae isolates would become sufficiently permeabilized, making some of their DNA accessible to added polymerase and primers. Further, we hypothesized that this accessible DNA would be detectable directly by isothermal amplification methods that do not fully lyse bacterial cells. We build on these results to develop the polymerase-accessibility AST (pol-aAST), a new phenotypic approach for β-lactams, the major antibiotic class for gram-negative infections. We test isolates of the 3 causative pathogens of CRE infections using ceftriaxone (CRO), ertapenem (ETP), and meropenem (MEM) and demonstrate agreement with gold-standard AST. Importantly, pol-aAST correctly categorized resistant isolates that are undetectable by current genotypic methods (negative for β-lactamase genes or lacking predictive genotypes). We also test contrived and clinical urine samples. We show that the pol-aAST can be performed in 30 min sample-to-answer using contrived urine samples and has the potential to be performed directly on clinical urine specimens.

1549. Impact of New Fluoroquinolone Breakpoints on Enterobacteriaceae Susceptibility Rates and Clinical Outcomes

BackgroundIn January 2019, the Clinical and Laboratory Standards Institute (CLSI) lowered the Fluoroquinolone (FQ) susceptibility breakpoints for Enterobacteriaceae. The new breakpoints were updated primarily based on FQ pharmacodynamics, and only limited clinical data. We sought to evaluate clinical outcomes among patients who received an FQ for infection with Enterobacteriaceae with MIC values that would now be considered resistant, using the new interpretive criteria. We also assessed the potential impact of the new breakpoints on overall blood and urine Enterobacteriaceae susceptibility rates at our medical center.MethodsAll positive blood and urine cultures with Enterobacteriaceae between September 1, 2018 and February 28, 2019 were included. Enterobacteriaceae isolates with ciprofloxacin MICs of 0.5 and 1 µg/mL (based on new breakpoints, now considered non-susceptible) were identified. We assessed the length of stay (LOS), mortality, and 30-day readmissions among patients who received an FQ for treatment. The impact of the new breakpoints on overall Enterobacteriaceae susceptibilities from urine and blood isolates was also determined.ResultsA total of 1,761 cultures (191 blood, 1,570 urine) grew Enterobacteriaceae. One-hundred and twenty-five (7%) cultures grew isolates with a ciprofloxacin MIC of 0.5 or 1 µg/mL. Eighteen patients with Enterobacteriaceae isolated (4 blood, 14 urine) received an FQ. Among these patients, the median LOS was 4 days; one patient was readmitted within 30 days, and 0% mortality was observed. The patient readmitted within 30 days received an FQ for a blood isolate with MIC 0.5. Overall, with the revised breakpoints, we observed a 4.2% decrease in the number of Enterobacteriaceae that would be susceptible to ciprofloxacin (Figure 1).ConclusionThe new FQ breakpoints for Enterobacteriaceae will have a marginal impact on overall FQ susceptibility rates at our medical center. In this single-center study, patients that received FQ antibiotics for Enterobacteriaceae with MIC values now considered intermediate or resistant did not appear to experience poor outcomes. Disclosures All authors: No reported disclosures.

Impact of Early Exposure to Cefuroxime on the Composition of the Gut Microbiota in Infants Following Cesarean Delivery

To assess in mothers giving birth by cesarean delivery if prophylactic antibiotics administered either before skin incision or immediately after cutting the umbilical cord influences gut microbiota colonization and antibiotic susceptibility of the gut bacteria in the newborn. Forty-two pregnant women scheduled for elective cesarean delivery were recruited at Odense University Hospital, Denmark, and randomly assigned to receive cefuroxime either before skin incision or immediately after the umbilical cord was cut. Fecal samples were collected from all infants at age 10days and 9months. Composition of the gut microbiota was determined by 16S ribosomal RNA gene amplicon high-throughput sequencing. Gram-positive cocci and Enterobacteriaceae were isolated and identified before antimicrobial susceptibility tests were performed by disk diffusion. No clear difference in the composition of the gut microbiota was observed between infants whose mothers received cefuroxime before or after cesarean delivery at neither time point, though surprisingly at 9months of age, but not at 10days of age, the number of observed species was higher in infants where mothers received cefuroxime after cord clamping. No differences in antimicrobial susceptibility of Enterobacteriaceae, Enterococcus spp, and Staphylococcus spp were seen at 10days. Timing of cefuroxime administration to mothers undergoing cesarean delivery does not have a major effect on the gut microbiota and bacterial antibiotic resistance traits in infants. Clinicaltrials.gov: NCT02072798.

Management of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections (MBI-LCBIs) in Stem Cell Transplant Recipients: A National Survey of Cancer Centers Practices

Background Patients with hematologic malignancies receiving chemotherapy and those undergoing stem cell transplantation (SCT) are at risk for mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBIs). Our comprehensive cancer center, which performs over 300 SCTs per year, has historically removed central venous catheters (CVCs) for the majority of transient MBI- LCBI cases in SCT recipients. However, given the lack of evidence-based guidelines for removal or salvage, we created a national survey to gauge current clinical practice of MBI-LCBI and CVC management among U.S. cancer centers. Methods We created a 22-item online anonymous survey via Qualtrics software. The survey was performed in August and September of 2018 and open for a total of 30 days. The questionnaire consisted of three parts: respondents' characteristics, MBI-LCBI and CVC clinical practice questions, and two clinical vignettes. In parallel, a quality improvement project is ongoing to evaluate outcomes following catheter salvage versus removal in MBI-LCBI cases of SCT recipients. Results The survey was distributed to seventy Infectious Diseases consultants at cancer centers in the United States. The response rate was 44%. 70% of respondents had > 5 years of clinical experience. The majority (75%) responded that MBI-LCBI does not implicate the CVC as the source of bacteremia. 61% of respondents salvage CVCs in SCT patients unless contraindicated. In patients with salvaged CVCs, 37.5% of responders do not use adjunct lock therapy and 46% deem repeat end of therapy surveillance blood culture as unnecessary. 62.5% of responders do not routinely recommend other procedures such as venous duplex ultrasound and transthoracic echocardiogram for MBI-LCBI cases unless clinically indicated. Among 90% of respondents deemed fluoroquinolone step down oral therapy for susceptible Enterobacteriaceae MBI-LCBI as acceptable. Conclusion Management of MBI-LCBIs in hematologic malignancies and SCT patients is variable but CVC salvage is considered by a majority of survey respondents as a safe approach. Data comparing outcomes of catheter salvage strategies are lacking. Results of our ongoing quality improvement project will provide further guidance.

1814. External Validation of Precision Antibiotic Therapy for Enterococcal Bloodstream Infections

BackgroundILÚM Heath Solutions, an infectious diseases software platform, developed precision antibiotic therapy (PAT) software to guide selection of therapy using data science, patient-specific factors, as well as historical patient, pharmacy, and microbiologic data. PAT reports percentages reflecting likelihood of susceptibility across a panel of antibiotics, identifying patients at high risk for resistant organisms. PAT has previously demonstrated high accuracy for predicting susceptibility of Enterobacteriaceae in bloodstream infections (BSIs) and risk for multi-drug resistance. The objective of this study was to validate PAT predictive capabilities in enterococcal BSIs and to assess accuracy in risk-stratifying patients for vancomycin-resistant Enterococcus spp. (VRE).MethodsThis retrospective cohort study included patients with an index enterococcal BSI from January 2016 through December 2016. The primary outcome was the performance characteristics of PAT in accurately predicting the risk of VRE, elaborated with sensitivity and specificity rates across varying PAT thresholds. Receiver operating characteristics (ROC) curve analyses were performed to identify an acceptable PAT threshold to define high risk for VRE. Brier score calculations were used to compare accuracy of PAT predictions to that of the institutional antibiogram.ResultsROC curve analysis (Figure 1) demonstrated an area under the curve of 0.94, indicating excellent discrimination. The Brier scores for the institutional antibiogram and PAT software were 0.067 and 0.075, respectively, representing a similar degree in accuracy. Species-level Brier scores for the institutional antibiogram and PAT were 0.043 and 0.065, respectively, for E. faecalis and 0.093 and 0.073, respectively, for E. faecium.Figure 1.ConclusionPAT software was able to discriminate enterococcal BSIs resistant and susceptible to vancomycin. Similar to previous results seen with Enterobacteriaceae, PAT may be useful to accurately predict susceptibilities for Enterococcus spp., particularly for E. faecium.Disclosures S. Overly, ILÚM Health Solutions: Consultant, Salary. J. Mehta, ILUM Health Solutions: Consultant, Salary.

2416. Risk Factors and Outcomes of Bacteremia Caused by Carbapenem-Resistant Enterobacteriaceae Compared With Carbapenem Susceptible Enterobacteriaceae

BackgroundDue to shrinking therapeutic options, infections due to Carbapenem-resistant enterobacteriaceae (CRE) are an urgent threat in healthcare systems across the world. While the CRE phenotype is determined by a number a different genes, the metallo β-lactamases such as the NDM, are particularly prevalent in the South Asian region. Data regarding infections with CRE caused by these strains is relatively limited. Our objective was to compare the risk factors and outcomes (mortality and length of hospitalization) of bacteremia secondary to CRE with bacteremia secondary to carbapenem susceptible enterobacteriaceae (CSE).MethodsWe conducted a cross-sectional study on patients admitted between 2013 and 2016, to a large tertiary care hospital in Karachi, Pakistan. Patients with CRE bacteremia were matched for the same year with patients with bacteremia due to CSE. Patients with polymicrobial blood cultures were excluded. Clinical data of these patients were obtained using a structured performa.ResultsA total of 131 patients were enrolled (65 CRE and 66 CSE). The mean age was similar in both groups (51.8 years and 57.1 years in CRE and CSE patients respectively). Compared with CSE, CRE bacteremia was more likely to occur in patients with Diabetes Mellitus or those with a tracheostomy (P = 0.002 and 0.014, respectively). The most common source of CRE bacteremia was central line associated (24.6% of all cases) as opposed to urinary tract infections in those with CSE bacteremia (62.1% of all cases). Fewer patients with CRE bacteremia received appropriate antibiotics (72.3% vs. 81.8%). Mortality was over three times higher in patients with CRE (41.5% vs. 12.1%, P = 0.001). The mortality remained higher when adjusted for the severity of illness using the PITT-bacteremia score. Increased mortality was also associated with central venous catheterization in both CRE and CSE bacteremia, while urinary catheterization and hemodialysis were associated with mortality in patients in CSE bacteremia only. While length of ICU stay was similar between the two groups, the median length of hospital stay was longer in patients with CRE (median of 8 days vs. 6 days, P = 0.021)ConclusionCRE bacteremia was more likely associated with central lines and led to significantly higher mortality and length of stay.Disclosures All authors: No reported disclosures.

1182. Risk Factors for the Acquisition of IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan: A Matched Case–control Study

BackgroundThe majority of CRE in Japan are IMP-type carbapenemase-producing CRE (IMP-CRE). However, research on risk factors for the acquisition of IMP-CRE has been limited, and questions exist regarding whether IMP-CRE have risk factors similar to other types of CRE such as KPC.MethodsWe conducted a matched case–control study involving patients from whom IMP-CRE had been isolated. The controls were selected among patients with carbapenem susceptible Enterobacteriaceae (CSE). Non-meropenem-susceptible per CLSI criteria and/or ceftazidime-resistant Enterobacteriaceae were screened, and metallo-β-lactamase–positive isolates were examined for blaIMP by PCR (January 2012 to December 2016).ResultsNinety-six patients with CRE were matched with 96 patients with CSE. They comprised Enterobacter sp. (n = 132 [CRE: 66, CSE: 66], 68.8%) and Klebsiella pneumoniae (n = 60 [CRE:30, CSE:30], 31.2%), and bacteria were most commonly isolated from sputum (n = 76 [39.6%]), followed by urine (n = 62 [32.3%]). Background factors such as age (median = 75 [IQR: 66–84]), sex (male = 56.8%), and the Charlson comorbidity index (median = 2 [IQR: 1–3.8]) were similar between CRE and CSE. In multivariate analysis, independent risk factors were identified: history of gastrointestinal (GI) endoscopy or surgery, history of ICU stay, and a previous exposure within 1 month to penicillins with β-lactamase inhibitors, cephalosporines, or carbapabnems.ConclusionHistories of GI endoscopy and ICU stay as well as broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Infection control measures combined with enhanced antimicrobial stewardship are key to preventing the spread of IMP-CRE. Multivariate analysis of risk factors for isolation of IMP-CRE , n (%)VariablesCRE(n = 96)CSE(n = 96)Adjusted odds ratio(95% CI)AdjustedP-valueHistoryGI endoscopy or surgery28 (29)12 (13)3.03 (1.24–7.43)0.015ICU stay32 (33)18 (19)2.25 (1.0–5.04)0.049Device useNasogastric tube43 (45)24 (25)1.27 (0.58–2.78)0.547Urinary catheter59 (61)38 (40)1.66 (0.83–3.33)0.155Tracheotomy18 (19)7 (7)2.17 (0.71–6.59)0.172PEG tube10 (10)3 (3)3.89 (0.74–20.57)0.11Antibiotic exposure ≤1 monthPenicillins with β-lactamase inhibitors52 (54)27 (28)4.54 (2.17–9.49)<0.001Cephalosporines40 (42)19 (20)3.38 (1.54–7.43)0.002Carbapenems25 (26)10 (10)3.08 (1.24–7.66)0.015Disclosures All authors: No reported disclosures.

Epidemiology of Diabetic Foot Infection in the Metro-Detroit Area With a Focus on Independent Predictors for Pathogens Resistant to Recommended Empiric Antimicrobial Therapy.

BackgroundThe polymicrobial nature of diabetic foot infection (DFI) and the emergence of antimicrobial resistance have complicated DFI treatment. Current treatment guidelines for deep DFI recommend coverage of methicillin-resistant Staphylococcus aureus (MRSA) and susceptible Enterobacteriaceae. This study aimed to describe the epidemiology of DFI and to identify predictors for DFI associated with multidrug-resistant organisms (MDROs) and pathogens resistant to recommended treatment (PRRT).MethodsAdult patients admitted to Detroit Medical Center from January 2012 to December 2015 with DFI and positive cultures were included. Demographics, comorbidities, microbiological history, sepsis severity, and antimicrobial use within 3 months before DFI were obtained retrospectively. DFI-PRRT was defined as a DFI associated with a pathogen resistant to both vancomycin and ceftriaxone. DFI-MDRO pathogens included MRSA in addition to PRRT.ResultsSix-hundred forty-eight unique patients were included, with a mean age of 58.4 ± 13.7 years. DFI-MDRO accounted for 364 (56%) of the cohort, and 194 (30%) patients had DFI-PRRT. Independent predictors for DFI-PRRT included history of PRRT in a diabetic foot ulcer, antimicrobial exposure in the prior 90 days, peripheral vascular disease, and chronic kidney disease. Long-term care facility residence was independently associated with DFI due to ceftriaxone-resistant Enterobacteriaceae, and recent hospitalization was an independent predictor of DFI due to vancomycin-resistant Enterococcus.ConclusionsAn unexpectedly high prevalence of DFI-PRRT pathogens was identified. History of the same pathogen in a prior diabetic foot ulcer and recent antimicrobial exposure were independent predictors of DFI-PRRT and should be considered when selecting empiric DFI therapy.

Evaluation of the Rapid Polymyxin NP test for detection of colistin susceptibility in Enterobacteriaceae isolated from Thai patients

Development and evaluations of the Rapid Polymyxin NP test for detection of colistin resistance in Enterobacteriaceae have been recently reported. In this study, we evaluated the performance of the test using a larger number of Enterobacteriaceae, and a larger proportion of isolates with a colistin MIC close to the breakpoint. Out of 339 isolates, the Rapid Polymyxin NP test detected colistin resistance in 13 isolates of Escherichia coli, 213 isolates of Klebsiella pneumoniae, 9 isolates of Enterobacter aerogenes, and 10 isolates of the other Enterobacteriaceae species. Sensitivity and specificity of the test for detecting colistin resistance were 100% and 95.9%, respectively. Positive predictive value and negative predictive value were 98.3% and 100%, respectively.

Rapid detection of carbapenemase-producing Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae using a bioluminescence-based phenotypic method

Accurate detection of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing carbapenem-resistant Acinetobacter spp. (CP-CRA) constitutes a major challenge in laboratory diagnostics. We developed a bioluminescence-based carbapenem susceptibility detection assay (BCDA) which allows identification of CRE (carbapenemase-producing-CRE (CP-CRE) as well as non-carbapenemase-producing-CRE (non-CP-CRE) and CP-CRA in 2.5 h from culture media. This laboratory method was evaluated with CP-CRE and CP-CRA isolates producing different β-lactamases of different Ambler classes (A, n = 16; B, n = 25; D, n = 67) and 22 non-CP-CRE. The results were correlated with those obtained by BD Phoenix™ and genotypic analysis results. The performance of BCDA on 123 validated CRE (except C. freundii isolates) and CP-CPA isolates revealed that 122 of 123 isolates were identified correctly. Only one OXA-48-producing Klebsiella pneumoniae was falsely classified. Among 45 meropenem susceptible Enterobacteriaceae (except C. freundii isolates) and meropenem susceptible Acinetobacter spp. strains tested, 44 were confirmed as susceptible by our BCDA. Overall, our BCDA had a sensitivity of 99% and a specificity of 98% and is a rapid and accurate assay which distinguished CRE/CP-CRA from meropenem susceptible Enterobacteriaceae and Acinetobacter spp.

Enterobacteriaceae susceptibility to piperacillin/tazobactam in a Chilean pediatric hospital

Enterobacteriaceae are a group of gram-negative rods that can cause serious infections in humans. A susceptibility in Klebsiella pneumoniae of 79.4% to piperacillin/tazobactam (PIP/TAZO) is reported in pediatric hospitals in Chile. There is no published data published to date regarding PIP/TAZO susceptibility to other Enterobacteriaceae species in this population. To measure the in vitro PIP/TAZO susceptibility in Enterobacteriaceae isolates from patients in a pediatric hospital in Chile. Descriptive and prospective study of Enterobacteriaceae positive cultures from patients assisting to the "Hospital de niños Roberto del Río" (HRRIO) between January 2013 and August 2014. PIP/TAZO susceptibility was established by gradient diffusion method (E-test®) according to the 2014 CLSI standards. 163 cases were included. The average age was 4 years and 15 days. 70.6% were female. 79.7% of samples were urine cultures. PIP/TAZO susceptibility in Enterobacteriaceae was 95.1% (n = 155). The intermediate susceptibility was 1.8% (n = 3). The isolates studied present high susceptibility to PIP/TAZO. This finding could be explained by the fact that this population has not been exposed to this antimicrobial therapy and also the low rates for ESBL in pediatric infections.

Ertapenem resistance in 2 tertiary-care hospitals: Microbiology, epidemiology, and risk factors

IntroductionCarbapenems resistance is a growing phenomenon and a threat to public health because of the reduced therapeutic options for resistant infections. MethodsA retrospective case–control study was conducted in 2 tertiary-care hospitals in Medellín, Colombia. Fifty patients infected with ertapenem-resistant enterobacteriaceae were compared with a control group consisting of 100 patients with infections caused by ertapenem susceptible enterobacteriaceae. A multivariate logistic regression model was used to identify factors that best explain ertapenem-resistant enterobacteriaceae infections. ResultsThe factors associated with ertapenem-resistant enterobacteriaceae infections were prior exposure to carbapenems (adjusted OR 3.43; 95% IC 1.08–10.87) and prior exposure to cefepime (adjusted OR 6.46; 95% IC 1.08–38.38). ConclusionPrior exposure to antibiotics is the factor that best explains the ertapenem-resistant enterobacteriaceae infection in this population, highlighting the importance of antimicrobial stewardship programs in hospitals.