Background Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. Methods An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed. Results Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 days (95% confidence interval [CI], -1.38 to -.41); linezolid: -0.89 days (95% CI, -1.27 to -.52); meropenem: -0.97 days (95% CI, -1.39 to -.56); tigecycline: -1.41 days (95% CI, -2.19 to -.63); P < .001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (-43.49; 95% CI, -58.61 to -28.37; P < .001), tigecycline (-35.47; 95% CI, -44.94 to -26.00; P < .001), and daptomycin (-9.47; 95% CI, -15.25 to -3.68; P = .002). Discussion A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.

Extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ec infections. To address the paucity of recent ESC-R-Ec molecular epidemiology data in the United States, we used whole-genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ec at a tertiary care cancer center in Houston, Texas, collected from 2016 to 2020. During the study time frame, there were 1,154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. Using time series analyses, we identified a temporal dynamic of ESC-R-Ec distinct from ESC-susceptible E. coli (ESC-S-Ec), with cases peaking in the last 6 months of the calendar year. WGS of 297 ESC-R-Ec strains revealed that while STc131 strains accounted for ~45% of total BSIs, the proportion of STc131 strains remained stable across the study time frame with infection peaks driven by genetically heterogeneous ESC-R-Ec clonal complexes. bla CTX-M variants accounted for most β-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R-Ec), and amplification of bla CTX-M genes was widely detected in ESC-R-Ec strains, particularly in carbapenem non-susceptible, recurrent BSI strains. Bla CTX-M-55 was significantly enriched within phylogroup A strains, and we identified bla CTX-M-55 plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R-Ec infections at a large tertiary care cancer center and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens. IMPORTANCE Given that E. coli is the leading cause of worldwide ESC-R Enterobacterales infections, we sought to assess the current molecular epidemiology of ESC-R-Ec using a WGS analysis of many BSIs over a 5-year period. We identified fluctuating temporal dynamics of ESC-R-Ec infections, which have also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of STc131 over the study period and demonstrate a limited but genetically diverse group of ESC-R-Ec clonal complexes are detected during infection peaks. Additionally, we provide a widespread assessment of β-lactamase gene copy number in ESC-R-Ec infections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R-Ec strains. These data suggest that serious ESC-R-Ec infections are driven by a diverse array of strains in our cohort and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures.

ABSTRACTExtended-spectrum cephalosporin resistantEscherichia coli(ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ecinfections. To address the paucity of recent ESC-R-Ecmolecular epidemiology data in the United States, we used whole genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ecat a tertiary care cancer center in Houston, Texas collected from 2016-2020. During the study timeframe, there were 1154 indexE. colibloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. Using time series analyses, we identified a temporal dynamic of ESC-R-Ecdistinct from ESC-susceptibleE. coli(ESC-S-Ec), with cases peaking in the last six months of the calendar year. WGS of 297 ESC-R-Ecstrains revealed that while STc131 strains accounted for ∼45% of total BSIs, the proportion of STc131 strains remained stable across the study time frame with infection peaks driven by genetically heterogeneous ESC-R-Ecclonal complexes.BlaCTX-Mvariants accounted for most β-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R-Ec), and amplification ofblaCTX-Mgenes was widely detected in ESC-R-Ecstrains, particularly in carbapenem non-susceptible, recurrent BSI strains.BlaCTX-M-55was significantly enriched within phylogroup A strains, and we identifiedblaCTX-M-55plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R-Ecinfections at a large tertiary care cancer center and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens.IMPORTANCEGiven thatE. coliis the leading cause of worldwide ESC-REnterobacteralesinfections, we sought to assess the current molecular epidemiology of ESC-R-Ecusing a WGS analysis of many BSIs over a five-year period. We identified fluctuating temporal dynamics of ESC-R-Ecinfections, which has also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of STc131 over the study period and demonstrate a limited, but genetically diverse group of ESC-R-Ecclonal complexes are detected during infection peaks. Additionally, we provide a widespread assessment of β-lactamase gene copy number in ESC-R-Ecinfections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R-Ecstrains. These data suggest that serious ESC-R-Ecinfections are driven by a diverse array of strains in our cohort and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures.

Extended-spectrum cephalosporin resistant Escherichia coli (ESC-R- Ec ) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R- Ec infections. To address the paucity of recent ESC-R- Ec molecular epidemiology data in the United States, we used whole genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R- Ec at a tertiary care cancer center in Houston, Texas collected from 2016-2020. During the study timeframe, there were 1154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R- Ec . Using time series analyses, we identified a temporal dynamic of ESC-R- Ec distinct from ESC-susceptible E. coli (ESC-S- Ec ), with cases peaking in the last six months of the calendar year. WGS of 297 ESC-R- Ec strains revealed that while STc131 strains accounted for ∼45% of total BSIs, the proportion of STc131 strains remained stable across the study time frame with infection peaks driven by genetically heterogeneous ESC-R- Ec clonal complexes. BlaCTX-M variants accounted for most β-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R -Ec ), and amplification of blaCTX-M genes was widely detected in ESC-R- Ec strains, particularly in carbapenem non-susceptible, recurrent BSI strains. BlaCTX-M-55 was significantly enriched within phylogroup A strains, and we identified blaCTX-M-55 plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R- Ec infections at a large tertiary care cancer center and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens.Given that E. coli is the leading cause of worldwide ESC-R Enterobacterales infections, we sought to assess the current molecular epidemiology of ESC-R- Ec using a WGS analysis of many BSIs over a five-year period. We identified fluctuating temporal dynamics of ESC-R- Ec infections, which has also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of STc131 over the study period and demonstrate a limited, but genetically diverse group of ESC-R- Ec clonal complexes are detected during infection peaks. Additionally, we provide a widespread assessment of β-lactamase gene copy number in ESC-R- Ec infections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R- Ec strains. These data suggest that serious ESC-R- Ec infections are driven by a diverse array of strains in our cohort and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures.

Locke, Shyanne1; Aitken, Samuel1; McDaneld, Patrick1; Bruno, Jeffrey2 Author Information

Purpose. To summarize the most highly esteemed, peer-reviewed, infectious diseases (ID) pharmacotherapy articles published in 2020. Summary. Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were deemed to have noteworthy contributions to ID pharmacotherapy in 2020, including those on coronavirus disease 2019 (COVID-19) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). To select the most significant articles of 2020, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) to vote on their top 10 articles of general ID and COVID-19 pharmacotherapy and one noteworthy HIV/AIDS publication. A total of 40 articles were nominated by HIDN: 35 articles pertaining to general ID/COVID-19 pharmacotherapy and 5 articles with HIV/AIDS involvement. Of the 247 SIDP members who responded to the survey, 205 and 42 members voted for general ID/COVID-19 pharmacotherapy articles and HIV/AIDS related articles, respectively. The top publications are summarized. Conclusion. In a taxing year of a global pandemic, the abundant and rapid distribution of ID literature has made it challenging for clinicians to stay informed of significant publications across the ID spectrum. This review summarizes significant ID-related publications in 2020 with the goal of aiding clinicians in staying up to date on the most relevant publications in ID pharmacotherapy.

Posaconazole (POS) appears to have dose-proportional pharmacokinetics; however, there is a paucity of real-life data. We retrospectively evaluated 67 patients with hematologic cancer who had POS dose increases from 300 mg/day to either 400 mg/day (n = 52) or 300 mg twice daily (BID) (n = 15) and for whom POS serum levels were measured. Median POS levels were 840 ng/ml, 1,625 ng/ml, and 2,710 ng/ml for the dosages of 300 mg/day, 400 mg/day, and 300 mg BID, respectively. Significant interpatient variability in serum levels was noted.

Background and Objectives : Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. Methods : We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the quality of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. Results : Completeness of ID provider notes improved from a baseline of 77% to 100% (p<.0001) for antimicrobial recommendations, 75% to 97% (p<.0001) for follow-up recommendations, and 19% to 98% (p<.0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24% to 56% (p=.027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. Conclusions : Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

Purpose To provide a summary of the most prominent peer-reviewed infectious diseases (ID) pharmacotherapy and Human Immunodeficiency Virus (HIV)-related articles published in 2019. Summary Houston Infectious Diseases Network (HIDN) members were asked to nominate articles that they believed were most influential within the ID and HIV pharmacotherapy science communities. A total of 48 general ID and 6 HIV-related articles were nominated. Following nominations, an online survey was distributed via e-mail to Society of Infectious Diseases Pharmacists (SIDP) members, with a total of 156 and 54 members voting for general ID and HIV-related articles, respectively. The results of this survey were ranked to determine the top 10 general ID and top HIV articles. The top articles were then summarized by HIDN members, including residents, fellows, and clinical pharmacists. Conclusion This review covers many of the most influential ID articles published in 2019, including 3 practice guideline updates. Due to the high rate of ID literature published each year, this review continues to help summarize these articles for the ID community, allowing clinicians to remain up-to-date on practice-changing publications in ID and HIV pharmacotherapy.

Abstract Background There are several clinical tools that have been developed to predict the likelihood of extended-spectrum β-lactamase producing Enterobacterales; however, the creation of these tools included few patients with cancer or otherwise immunosuppressed. The objectives of this retrospective cohort study were to develop a decision tree and traditional risk score to predict ceftriaxone resistance in cancer patients with Escherichia coli (E. coli) bacteremia as well as to compare the predictive accuracy between the tools. Methods Adults age ≥ 18 years old with E. coli bacteremia at The University of Texas MD Anderson Cancer Center from 1/2018 to 12/2019 were included. Isolates recovered within 1 week from the same patient were excluded. The decision tree was constructed using classification and regression tree analysis, with a minimum node size of 10. The risk score was created using a multivariable logistic regression model derived by using stepwise variable selection with backward elimination at level 0.2. The decision tree and risk score statistical metrics were compared. Results A total of 629 E. coli isolates were screened, of which 580 isolates met criteria. Ceftriaxone-resistant (CRO-R) E. coli accounted for 36% of isolates. The machine learning-derived decision tree included 5 predictors whereas the logistic regression-derived risk score included 7 predictors. The risk score cutoff point of ≥ 5 points demonstrated the most optimized overall classification accuracy. The positive predictive value of the decision tree was higher than that of the risk score (88% vs 74%, respectively), but the area under the receiver operating characteristic curve and model accuracy of the risk score was higher than that of the decision tree (0.85 vs 0.73 and 82% vs 74%, respectively). Figure 1. Clinical Decision Tree Table 1. Regression Model and Assigned Points for Clinical Risk Score Table 2. Statistical Metrics of Clinical Decision Tree and Clinical Risk Score Conclusion The decision tree and risk score can be used to determine the likelihood of whether a cancer patient with E. coli bacteremia has a CRO-R infection. In both clinical tools, the strongest predictor was a history of CRO-R E. coli colonization or infection in the last 6 months. The decision tree was more user-friendly, has fewer variables, and has a better positive predictive value in comparison to the risk score. However, the risk score has a significantly better discrimination and model accuracy than that of the decision tree. Disclosures Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support

Background and objectives Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. Methods We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the completeness of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. Results Completeness of ID provider notes improved from a baseline of 77 to 100% ( p < .0001) for antimicrobial recommendations, 75 to 97% ( p < .0001) for follow-up recommendations, and 19 to 98% ( p < .0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24 to 56% ( p = .027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. Conclusions Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

OPAT helps reduce hospital length of stay, but 1 in 4 patients is readmitted within 30 days of discharge. Follow up < 30 days after discharge and laboratory monitoring during therapy have been shown to reduce hospital readmissions. However, few OPAT studies have included patients with malignancies, who may not experience the same benefits due to increased risks for hospital admission and infection related to antineoplastic therapy. We started an OPAT program to increase laboratory monitoring and clinic follow up among patients with solid tumors, attempting to also decrease readmissions. We obtained demographic data and baseline frequencies of laboratory monitoring, ID clinic follow up, 30-day OPAT-related readmissions, Emergency Center (EC) visits, and deaths by retrospective chart review. We conducted multiple interventions from June 2018-January 2020: clarifying physician recommendations for laboratory monitoring and follow up by using a standardized electronic medical record template, communicating recommendations to case management, and changing the lab ordering workflow. We compared frequencies after interventions to baseline by using Fisher’s exact test. Most commonly observed malignancies in our patient cohort included genitourinary, breast, gastrointestinal, gynecologic, and head and neck. The most commonly treated infections included abscess, bacteremia, and skin and soft tissue. The percentage of patients without recommended lab monitoring decreased from 32.3% to 15.3% (p=0.03). We observed trends toward improved ID clinic follow up (54.8% to 71.8%; p=0.12) and decreased 30-day OPAT-related readmissions from 16.7% to 8.6% (p = 0.17). We observed no difference in mortality or EC visits. OPAT-treated infections in our solid tumor patient cohort differed from those reported commonly. Through continued interventions, we improved lab monitoring rates among solid tumor patients with trends toward improved ID clinic follow up and decreased readmission rates. Our findings suggest that despite competing reasons for hospital readmission, OPAT may still benefit this population. All Authors: No reported disclosures

Abstract Background Increasing rates of antimicrobial resistance require more frequent parenteral antimicrobial therapy. OPAT improves patient quality of life and is cost-effective. Although IDSA OPAT guidelines are applied to cancer patients, few studies have addressed implementation in this unique population. Through our quality improvement project, we aimed to improve monitoring of solid tumor patients recommended for OPAT by infectious diseases (ID) consultation as measured by an increased percentage of patients with physician follow-up and laboratory monitoring. Methods We used the plan-do-study-act methodology to guide our quality improvement project. To establish baseline frequencies, we retrospectively reviewed a subset of solid tumor patients seen for ID consultation and recommended for OPAT. We used brainstorming, fishbone analysis, and process mapping to analyze our current process. We standardized a sign-off note for inclusion with OPAT recommendations within our electronic medical record. We reminded ID providers of the new process weekly and to notify the OPAT team and outpatient clinical nursing staff of OPAT-enrolled patients. Results We found that clarifying recommendations addressed several identified obstacles to monitoring. After instituting our intervention, the percentage of patients who completed follow-up increased from 44% to 78% during the 6-week intervention period. Although the frequency of laboratory monitoring recommendations increased from 43% to 86%, the percentage of patients completing such monitoring did not improve. Our results were sustainable during the 3-month post-intervention observation period. Conclusion By standardizing ID recommendations, we increased outpatient follow-up frequency. Our inability to increase the frequency of laboratory monitoring likely reflects the increased complexity of the process, which requires action from external stakeholders. We learned that a simple intervention can have a meaningful impact and that gains can be limited without involvement of all stakeholders. We plan to expand to a comprehensive OPAT clinic for all patients at our facility and further characterize challenges and opportunities for utilizing OPAT in cancer patients. Disclosures All authors: No reported disclosures.

Infections with extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli are common in patients with hematologic malignancy. The utility of cefepime and piperacillin-tazobactam as empiric therapy for ESBL-producing E. coli bacteremia in patients with hematologic malignancy is largely unknown.

Purpose: To summarize the top 10 most influential peer-reviewed infectious diseases (ID) pharmacotherapy articles published in the year 2018. Summary: Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were thought to have most notably contributed to ID pharmacotherapy in 2018, including those related to human immunodeficiency virus (HIV). A total of 26 articles were nominated: 22 articles pertaining to general ID pharmacotherapy and 4 articles involving HIV/AIDS. To select the most significant articles of 2018, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) asking members to vote on their top 10 general ID publications and 1 HIV publication. Of the 462 members surveyed, 213 (46%) and 108 (23%) voted for general ID pharmacotherapy- and HIV-related articles, respectively. The top article(s) for both categories are summarized. Conclusion: With the increased emphasis on antimicrobial stewardship initiatives and the growing problem of multidrug-resistant (MDR) organisms, the amount of ID literature centered on stewardship, appropriate treatment durations, and newly approved antimicrobial agents continues to expand, making it challenging for clinicians to stay informed on the most relevant publications. This review summarizes significant ID-related publications in 2018 with the goal of aiding clinicians in staying up to date on the most noteworthy publications in ID pharmacotherapy.

Abstract Background Dalbavancin (DAL) is a long-acting lipoglycopeptide, which allows for up to 2 weeks of therapy from a single dose. Outside of its FDA-approved indication for the treatment of acute bacterial skin and skin structure infections (ABSSSI), there is a growing interest in the utilization of DAL for other indications, including catheter-related bloodstream infection (CRBSI). The long-acting formulation potentially facilitates patient discharge or admission deferral without the need for daily outpatient parenteral antimicrobial therapy (OPAT). However, there is limited experience reporting DAL utilization in an oncology population. The objective of this study was to report our experience with DAL in an oncology patient population at a National Cancer Institute (NCI) Designated Cancer Center. Methods We conducted a retrospective review of all patients receiving DAL therapy in June 2016–June 2017. The primary outcome was a clinical success at 30 days (complete/partial resolution of symptoms without readmission for a same/similar infection), with secondary outcomes including readmission rate, acute kidney injury (AKI) incidence (Acute Kidney Injury Network [AKIN] criteria) and additional antimicrobial use within 30 days. Results We identified 76 unique subjects, with 77 unique infectious episodes, receiving 78 DAL doses. The majority of the subjects were male (57%), the median age was 61 years old, 55% had a solid tumor type and most were treated for ABSSSI (86%). Doses were administered inpatient 76% of the time and most patients received 1500 mg (90%). The most common pathogen isolated was Staphylococcus aureus (19%). Patients frequently received additional methicillin-resistant Staphylococcus aureus active oral antibiotics (39%). Clinical success was reported in 78% of infections. Potential DAL-related AKI was identified in 4 subjects (5%). Conclusion We reported on the use of DAL in a variety of oncology patients at a major cancer center. Clinical success was often achieved in ABSSSI with a single DAL dose and nephrotoxicity was infrequently encountered. Limitations include the frequent use of additional, potentially active antimicrobials and difficulty in assessment of clinical success and AKI in patients after discharge. Disclosures All authors: No reported disclosures.

Purpose: This is a summary of the most important articles on infectious diseases (ID) pharmacotherapy published in peer-reviewed literature in 2016 as selected by clinical pharmacists with ID expertise. Summary: The Houston Infectious Diseases Network (HIDN) was asked to identify articles published in peer-reviewed literature in 2016 that were believed to contribute significantly to ID pharmacotherapy, including human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). A list of 46 articles on general ID pharmacotherapy and 8 articles on HIV/AIDS were nominated. Members of the Society of Infectious Diseases Pharmacists (SIDP) were surveyed to select 10 general ID articles believed to have made a significant impact on general ID pharmacotherapy and 1 article most significant to HIV/AIDS pharmacotherapy. Of 445 SIDP members surveyed, 212 (47.6%) and 95 (21.3%) members voted for general ID pharmacotherapy- and HIV/AIDS-related articles, respectively. The 11 highest-ranked papers (10 general ID-related articles and 1 HIV/AIDS-related article) are summarized here. Conclusion: With the large number of ID-related articles published each year, it can be challenging to stay current with the most relevant ID publications. This review of significant publications in 2016 may provide a starting point for that process.

Abstract Background Carbapenems are the treatment of choice for bacteremia caused by extended spectrum β-lactamase producing Enterobacteriaceae (ESBL-E). The emergence carbapenem resistance (CR) in ESBL-E isolates has been described; however, the rate of such resistance in clinical settings is unknown. We describe the frequency and mechanisms of CR in recurrent ESBL-E bacteremia at an NCI-designated cancer center. Methods We performed a prospective whole genome sequencing (WGS) study and retrospective cohort review of adult (age ≥18 years) patients with ESBL-E bacteremia between January 2015 and July 2016. Recurrent bacteremia was defined as identification of the same organism in blood culture at any time following initial successful treatment. CR was defined as resistance to meropenem. Carbapenemase production was assessed in the microbiology laboratory using Carba-NP. Available paired isolates underwent WGS via Illumina HiSeq for assessment of clonality and identification of CR mechanisms. Results One hundred and sixteen patients with ESBL-E bacteremia were identified. E. coli was the most common organism (86%), followed by K. pneumoniae (12%), and K. oxytoca (2%). Recurrent bacteremia was identified in 17 (15%) patients (E. coli [n = 15], K. pneumoniae [n = 2]). Of these, 6 (35%) were CR and 5/6 (83%) were Carba-NP negative. All six recurrent CR isolates occurred in patients with leukemia. Five isolate pairs were available for WGS. In four of five pairs (three E. coli, one K. pneumoniae), CR emerged from the same strain causing the original infection; one recurrence was caused by a distinct E. coli with a OXA-48-like gene. Compared with parental strains, CR E. coli contained deletions in porin-encoding genes and had increased mapping depth for genes encoding CTX-M ESBLs. The K. pneumoniae was Carba-NP negative with no identifiable CR mechanism. Conclusion Emergence of CR following treatment for ESBL-E bacteremia was seen only in leukemia patients and was primarily due to porin loss and amplification of ESBL genes, rather than acquisition of exogenous carbapenemases. These are the first clinical data describing the molecular mechanism of ESBL-E transformation to CR. These data serve as the basis for future studies of antimicrobial stewardship interventions to limit the emergence of CR in ESBL-E. Disclosures S. L. Aitken, Shionogi: Scientific Advisor, Consulting fee. Medicines Company: Scientific Advisor, Consulting fee. Merck & Co.: Scientific Advisor, Consulting fee.

We read the recent paper by Cheng et al. with interest and commend the authors for assessing the clinically important question of whether piperacillin-tazobactam can be used as definitive therapy for bacteremia caused by Enterobacteriaceae harboring inducible AmpC β-lactamases ([1][1]). However, we