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Clinical Characteristics and Outcomes of Staphylococcus aureus Bacteremia from a Biliary Source

Eunmi Yang, MD – Resident, Asan Medical Center

Seongman Bae, MD – Fellow, Asan Medical Center

Hyeonji Seo, MD – Resident, Asan Medical Center

Eunbeen Cho, MD – Fellow, Asan Medical Center

Su-Jin Park, Doctor – Research scientist, Center for Antimicrobial Resistance and Microbial Genetics

Heungsup Sung, PhD – Professor, Asan Medical Center

Mi-Na Kim, PhD – Professor, Asan Medical Center

Jiwon Jung, MD – Assistant Professor, Asan Medical Center

Min Jae Kim, MD – Professor, Asan Medical Center

Sung-Han Kim, MD – Professor, Asan Medical Center

Sang-Oh Lee, MD – Professor, Asan Medical Center

Sang-Ho Choi, MD – Professor, Asan Medical Center

Jun Hee Woo, PhD – Professor, Asan Medical Center

Yang Soo Kim, MD – Professor, Asan Medical Center

Yong Pil Chong, MD – Professor, Asan Medical Center

Background :

Staphylococcus aureus can cause various types of infection, but involvement of biliary tract is rare. There were only few case reports and no clinical studies. We assessed the clinical characteristics and outcomes of S. aureus bacteremia from a biliary source (biliary SAB) in a large cohort of SAB patients and compared the cases with those of catheter-related SAB.

Methods :

We performed a matched case-control study within a prospective observational cohort of patients with SAB at a 2,700-bed tertiary hospital. All adult patients with SAB were observed for 12 weeks from July 2008 to July 2018. Biliary SAB was defined as the case of S.aureus isolated from blood culture with appropriate clinical biliary infection symptoms (fever, abdominal pain, or jaundice) and signs (abdominal tenderness or liver enzyme elevation with obstructive pattern). Biliary SAB cases were matched 1:3 to control patients with catheter-related SAB based on age, gender, ward, and case year.

Results :

A total of 1818 patients with SAB were enrolled in the entire cohort, and 42 (2%) were biliary SAB. Among patients with biliary SAB, 32 (76%) had solid tumor involving pancreaticobiliary tract or liver, 30 (71%) had biliary drainage stent, 14 (33%) were biliary procedure related infection, and 24 (57%) had recent broad-spectrum antibiotics exposure (Table1). When biliary SAB patients were compared with 126 patients with catheter-related SAB, they were significantly more likely to have community-onset SAB, solid tumor, and lower APACHE II score; and less likely to have metastatic infection (p = 0.03) (Table 2). Biliary SAB, solid tumor, and a high Charlson comorbidity index were associated with 12-week mortality. In multivariate analysis, biliary SAB (aOR, 5.5; 95% CI, 2.47 – 12.25) and a high Charlson comorbidity index (aOR, 1.32; 95% CI, 1.12 – 1.54) were independent risk factors for 12-week mortality.

Conclusion :

Biliary SAB was relatively rare and developed mainly in pancreaticobiliary cancer patients and in recent broad-spectrum antibiotic users. High mortality was probably attributable to underlying cancers. When biliary tract infection caused by S. aureus is clinically suspected, early aggressive treatment for SAB should be considered.

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Clinical Outcomes of Patients with Secondary Bacteremia in the Omadacycline Phase 3 Acute Bacterial Skin and Skin Structure Infections and Community-Acquired Bacterial Pneumonia Studies

George Sakoulas, MD – Associate Adjunct Professor, University of California, San Diego

Paul Eckburg, MD – Consultant, Self-employed

Amy Manley, BS – Executive Director, Clinical Operations, Paratek Pharmaceuticals, Inc.

Evan Tzanis, B.A. – Vice President, Chief Development Officer, Paratek Pharmaceuticals

Lynne Garrity-Ryan, PhD – Director, Scientific Affairs, Paratek Pharmaceuticals, Inc.

Anita F. Das, PhD – Statistician, Das Consulting

Marla Curran, DrPH – Executive Director, Head of Biometrics, Paratek Pharmaceuticals Inc.

Bob Noble, PhD – Director, Statistical Methods, Paratek Pharmaceuticals, Inc.

Paul McGovern, M.D. – Vice President, Paratek Pharmaceuticals

Background :

Low serum concentrations of tetracycline antibiotics may raise concerns on their efficacy in patients with secondary bacteremia, especially in comorbid patients and in those with higher acuity of illness. Omadacycline (OMC), an aminomethylcycline antibiotic, showed non-inferiority to linezolid (LZD) in two acute bacterial skin and skin structure infections (ABSSSI) studies (Omadacycline in Acute Skin and skin structure Infections Study [OASIS]-1 and 2), or to moxifloxacin (MOX) in a community-acquired bacterial pneumonia (CABP) study (Omadacycline for Pneumonia Treatment In the Community study [OPTIC]). This analysis considers clinical outcomes in patients with secondary bacteremia identified in these studies. 

Methods : Baseline blood cultures were taken from adult patients enrolled in Phase 3 randomized, double-blind clinical studies of OMC. Patients received ≥ 1 treatment dose: N=1,347 ABSSSI (OMC n=676; LZD n=671); N=774 CABP (OMC n=386; MOX n=388). Efficacy was evaluated by investigator assessment of clinical response at a post treatment evaluation (PTE) 7-14 days (ABSSSI) or 5-10 days (CABP) after last dose. 

Results : Bacteremia was confirmed in 63 patients (3%) across the three studies. Staphylococcus aureus was the most common pathogen in patients with ABSSSI (N=30: OMC n/N=7/13; LZD n/N=9/17), with a median treatment duration of median 9 days (OMC) and median 10 days (LZD). Streptococcus pneumoniae was the most common pathogen in patients with CABP (N=33; OMC n/N=11/15; MOX n/N=11/18), with median treatment durations of 11 days (OMC) and 14 days (MOX). Clinical success was numerically comparable between treatment groups within each study (Figure) after completion of therapy. 

Conclusion : The clinical successes of patients receiving OMC for ABSSSI or CABP with secondary bacteremia were comparable to results for LZD and MOX, respectively. Although limited by the small sample size, data from ABSSSI and CABP study patients with secondary bacteremia provide reassurance for use of OMC. Real-world OMC data in patients with ABSSSI and CABP will be needed to assess outcomes in patients with additional comorbidities and/or higher acuity of illness.

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Physiological Signature of Bloodstream Infection in Critically Ill Patients

Alex Zimmet, MD – Resident, University of Virginia Medical Center

Matthew Clark, PhD – Chief Science Officer, Advanced Medical Predictive Devices, Diagnostics, and Displays

Shrirang Gadrey, MD MPH – Assistant Professor, University of Virginia

Taison Bell, MD – Assistant Professor, UVa Health System

J. Randall Moorman, MD – Professor, University of Virginia

Christopher Moore, MD – Dr., University of Virginia

Background : Bloodstream infection (BSI) is associated with high mortality rates in critically ill patients but is difficult to identify clinically. This uncertainty results in frequent blood culture testing, which exposes patients to additional costs and the potential harms of unnecessary antibiotics. Accordingly, we aimed to identify signatures in physiological data from critically ill adults that characterize BSI.

Methods : We reviewed all blood culture, vital sign, laboratory, and cardiorespiratory monitoring (CRM) data from patients admitted to the medical and surgical/trauma ICUs at the University of Virginia Medical Center from February 2011 to June 2015. Blood culture results were categorized as positive, negative, or contaminant. For the BSI population, we included data obtained within 12 hours before or 24 hours after acquisition of a positive blood culture. The control population included data greater than 12 hours before or 24 hours after acquisition of a positive blood culture, and all data from patients without BSI. We used multivariable logistic regression to identify physiological characteristics of BSI.

Results : We analyzed 9,955 ICU admissions with 144 patient-years of vital sign and CRM data (1.3M hourly measurements). The average age was 59 years; the population was mostly Caucasian (81%) and male (56%). There were 5,671 (57%) admissions with ≥ 1 blood culture, and 744 (7%) had a BSI. The in-hospital mortality rate for patients with BSI was 28% vs. 12% for all others. The physiological signature of BSI was characterized by abnormalities in 12 parameters (Figure 1) – e.g., BSI was more likely in patients with higher pulse and lower platelets. Several associations were nonlinear – e.g., temperature and WBC had U-shaped relationships with BSI. The internally validated C-statistic was 0.77.

Conclusion : Statistical modeling revealed a clinically sensible physiological signature of BSI that could assist with bedside decisions regarding the utility of blood culture testing in critically ill adults.

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Understanding the Changes in Infective Endocarditis Admission in Pennsylvania During the Opioid Crisis

Jessica Meisner, MD, MS, MSHP – Post-Doctoral Fellow, University of Pennsylvania

Judith Anesi, MD – Instructor of Medicine, University of Pennsylvania

Xinwei Chen, MS – Statistical Analyst, Division of General Internal Medicine

Dave Grande, MD, MPA – Associate Professor of Medicine, University of Pennsylvania

Background : Nationwide, there has been a rise in cases of infective endocarditis (IE) correlating with the rise of the opioid crisis. Pennsylvania (PA) has the 3rd highest rate of drug overdose deaths in the country, with Allegheny & Philadelphia counties having the highest rates in the country. With this study, we evaluated how IE has changed in the face of the opioid crisis with respect to the population impacted & associated health care utilization in PA.

Methods : We performed a retrospective cohort study of all adults admitted to an acute care hospital in PA between 1/2013 & 3/2017 with a diagnosis of IE. Patients were identified through the Pennsylvania Health Care Cost Containment Council (PHC4) via billing codes. Exposed patients were those with drug use-associated IE (DU-IE); the unexposed group were those with non-DU-IE. We determined the number of admissions & geographical distribution of IE & DU-IE in the state. We then assessed for differences in hepatitis C (HCV) & HIV serostatus, length of stay (LOS), insurance status, total hospital charges, & rates of valve surgery between the two groups.

Results : There were 17,224 admissions for IE in PA during the study period, of which 11.2% were DU-IE. In Allegheny & Philadelphia counties, 14.4% & 20.5% were from DU-IE, respectively. DU-IE cases increased from 6% in 2013 to 17% in 2017, P < 0.001. We found several significant differences between the DU-IE & non-DU-IE groups: DU-IE group was younger (median 33 vs 69 years old, P < 0.001); the LOS was longer in the DU-IE group (10 vs 7 days, P < 0.001); the percentage of patients leaving Against Medical Advice was higher in DU-IE group (15.7% vs to 1.1%, P < 0.001); a higher proportion of the DU-IE group were HCV & HIV seropositive (27.1% vs 3.3% for HCV, 2.4% vs 0.74% for HIV, P < 0.001). See figures for complete results.

Conclusion : Pennsylvania had an increase in the number of IE cases over the last 4 years, driven by the opioid crisis, with Philadelphia & Alleghany counties being the most impacted areas. While this study is limited by the use of claims data, it demonstrates the downstream effects of the opioid crisis on the patient population at risk & the healthcare system due to longer & costlier hospital stays. This study supports the need for innovative & integrative care models to support them.

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Evaluation of the clinical Impact of the T2MR for the Diagnosis of Blood Stream Infections

Tamara Seitz, MD – Dr., SMZ SÜD Vienna, Department of Infectious Diseases and Tropical Medcine

Sebastian Baumgartner, MD – Dr., SMZ SÜD Vienna, Department of Infectious Diseases and Tropical Medcine

Christoph Wenisch, MD – Doz.Dr., SMZ Süd Vienna, Austria

Alexander Zoufaly, MD – Doz.Dr, SMZ SÜD Vienna, Austria

Background : The EK-189 study evaluates the clinical impact of T2 Magnetic Resonance (T2MR) for rapid detection of Blood Stream Infections (BSI) caused by ESKAPE-pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Escherichia coli) compared to blood culture (BC). Here we present preliminary results from this ongoing study.

Methods : Patients newly admitted to an infectious diseases department with suspected blood stream infection with ESKAPE pathogens (based on predefined criteria) are included and randomized into BSI diagnosis with a) T2MR and blood culture or b) blood culture alone. Routine diagnostic work-up including chest X-ray, complete lab work up (including blood count, C-reactive protein, interleukin-6) are performed in all patients. Antibiotic regimens are selected empirically based on suspected pathogens and are switched to targeted therapy at the discretion of the treating physician once a pathogen is detected. Outcome parameters include time to targeted (predefined) antibiotic therapy and time to discharge. Test characteristics of the T2MR compared to BC are also assessed.

Results : So far 44 patients were included (22 in each group). In 9/22 patients (41%) in the T2MR-group a pathogen was detected (4 Escherichia coli, 2 Klebsiella pneumoniae, 1 Staphylococcus aureus, 1 Pseudomonas aeruginosa and 1 Acinetobacter baumanii) and in 3/22 (14%) patients in the BC-group (all Escherichia coli).
The comparison of T2MR versus BC is depicted in table 1. Sensitivity and specificity of T2MR in comparison to BC was 100% and 64.7 %. All positive results in T2MR were considered true positive results.
The days until clinical improvement, the need for admission at ICU and the in-hospital mortality were similar in both groups.

Conclusion : The results from this preliminary analysis show that in patients with suspected BSI with ESKAPE pathogens, T2MR detects more pathogens than BC and potentially provides a quicker detection and shorter time to targeted therapy. Further analyses of this ongoing study with a larger sample size are needed to evaluate the impact of the use of T2MR on patient’s outcome

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Risk Factors and Clinical Outcomes of Carbapenem Non-susceptible Gram Negative Bacteremia in Patients with Acute Myelogenous Leukemia

Dong Hoon Shin, M.D. – Resident, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Kang Il Jun, M.D. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Song Mi Moon, M.D., PhD. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Wan Beom Park, M.D., PhD. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Ji Hwan Bang, M.D., PhD. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Eu Suk Kim, M.D., PhD. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Sang Won Park, M.D., PhD. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Hong Bin Kim, MD, PhD – Professor, Division of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

Nam-Joong Kim, M.D., PhD. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Chang Kyung Kang, M.D. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Myoung-don Oh, M.D., PhD. – Professor, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Background : Early administration of susceptible antibiotics is crucial in gram negative bacteremia (GNB), especially in immunocompromised patients. We aimed to explore risk factors and clinical outcomes of carbapenem non-susceptible (Carba-NS) GNB in patients with acute myelogenous leukemia (AML).

Methods : Cases of all GNB during induction or consolidation chemotherapy for AML in a 15-year period in a tertiary hospital were retrospectively reviewed. Independent risk factors for Carba-NS GNB were sought and its clinical outcomes were compared with those of carbapenem susceptible (Carba-S) GNB.

Results : Among 485 GNB cases from 930 patients, 440 (91%) were Carba-S and 45 (9%) were Carba-NS GNB. Frequent Carba-NS isolates were Stenotrophomonas maltophilia (n=23), Pseudomonas aeruginosa (n=11), and Acinetobacter baumannii (n=10). Independent risk factors for Carba-NS GNB were carbapenem use at the onset of GNB (aOR [95%CI], 78.6 [24.4-252.8]; P < 0.001), the isolation of imipenem resistant A. baumannii in the prior 1 year (aOR [95%CI], 14.6 [2.7-79.9]; P = 0.002), time interval from chemotherapy to GNB ≥ 20 days (aOR [95%CI], 4.7 [1.7-13.1]; P = 0.003), and length of hospital stay ≥ 30 days (aOR [95%CI], 3.4 [1.3-9.1]; P = 0.013). Except breakthrough GNBs which occurred during carbapenem treatment, the frequency of Carba-NS GNB was 48% (19/40) in cases having ≥ 2 risk factors other than carbapenem use. 30-day overall mortality (Carba-NS, 36% vs. Carba-S, 6%; P < 0.001) and in-hospital mortality (Carba-NS, 47% vs. Carba-S, 9%; P < 0.001) were significantly higher in Carba-NS GNB.

Conclusion : Carba-NS GNB in AML patients was independently associated with use of carbapenem, the past isolation of resistant organism, and late onset of GNB, and its clinical outcomes were poorer than those of Carba-S GNB. Carba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors.

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Hospitalized Burn Patients with Fever and Leukocytosis: Blood Culture or Not?

Ruihong Luo, MD, PhD – Assistant Clinical Professor, University of California Los Angeles

Paul Janoian, MD – Clinical Instructor, University of California Los Angeles

Background : Fever and leukocytosis are very common in patients with burn injury. Many patients had to do blood cultures frequently during their hospitalization given the concern of bacteremia. We opt to utilize the clinical characters of the patients to evaluate the risk for bacteremia and avoid unnecessary blood culture.

Methods : The adult patients (≥18 years) with burn injury were selected from the Nationwide Inpatient Sample database (2005-2014). Using ICD-9 codes, we further identified bacteremia, total body surface area (TBSA) of burn, inhalation injury, pneumonia, urinary tract infection, wound infection, escharotomy, placement of central venous line, indwelling urinary catheter, gastrostomy tube (G-tube), intubation, and total parenteral nutrition (TPN). The risk factors for bacteremia were evaluated by Logistic regression. A risk-adjusted model to predict the occurrence of bacteremia was developed by discriminant analysis.

Results : 241,323 hospitalized patients with burn injury were identified. The incidence of bacteremia was 1.1% (n=2,634). Comparing with the patients without bacteremia, those with bacteremia were older (51.1 vs. 46.7 year-old, p< 0.001), had more severe burn injury (50.7% vs. 12% with burn TBSA over 20%, p< 0.001) and comorbidities (22.7% vs. 14.9% with Charlson index ≥ 2, p< 0.001), higher in-hospital mortality (5.6% vs. 3.7%, p< 0.001), longer hospital stay (26 vs. 5 days, p< 0.001) and more hospital charges ($206,028 vs. $30,339, p< 0.001). When the age, sex, race, and Charlson index of the patients were adjusted by Logistic regression, it was found that the factors of inhalation injury (OR=1.25, 95% CI 1.03-1.51), intubation (OR=1.62, 95% CI 1.44-1.82), TPN (OR=1.56, 95% CI 1.16-2.11), placement of central venous line (OR=1.86, 95% 1.57-2.01) and G-tube (OR=2.04, 95% CI 1.60-2.60) were associated with increased risk for bacteremia. A risk-adjusted model composed of the patient’s age, Charlson index, burn TBSA, inhalation injury, intubation, TPN, placement of central venous line and G-tube could predict the occurrence of bacteremia with an accurate rate of 85.4% (Table 1).

Conclusion : The risk factors and risk-adjusted model for bacteremia may assist to decide whether a blood culture is needed in the hospitalized burn patients.

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Factors Associated with Positive Follow up Blood Cultures in Gram-Negative Septicemia

Orly Hadar, MD – Internal Medicine Resident, Cleveland Clinic Florida

Amy Van, MD candidate – Medical Student, Ross Medical School

Carla McWilliams, MD – Dr, Cleveland Clinic Florida

Luis Wulff, MD – Internal Medicine Resident, Cleveland Clinic Florida

Linda Godinez, MD – Internal Medicine, Cleveland Clinic Florida

Background :

Bloodstream infections remain a significant cause of morbidity and mortality. No guidelines for the management of non-catheter associated gram-negative septicemia exist. There is considerable debate regarding the role for follow up blood cultures. Studies have shown inadequate antibiotic therapy increases mortality in gram negative sepsis. We evaluated factors associated with a higher likelihood of positive follow up blood cultures (FUBC).

Methods :

A retrospective cohort study was conducted to look at factors associated with an increased likelihood of positive FUBC. Data was obtained via Epic chart review. Empiric antimicrobial regimens were reviewed in all patients with MDRO infections.

Results : We identified 1,527 patients ≥18 years admitted with gram-negative septicemia from 1/1/2013 through 1/1/2018. A total of 8.4% had positive FUBC. Patients with positive FUBC had a younger median age than the no growth group (64.7 vs. 69.4, p <0.001). Admission systolic blood pressure was lower in the group with positive FUBC than the no growth group (107 vs. 116, p=0.008). The odds ratio for positive FUBC for cardiac device was 2.08 (95% CI = [0.97, 4.35], p = 0.061); central line infection (vs. urinary tract infection) adjusted odds ratio was 2.08 (95% CI = [1.10, 3.95], p=0.025). The positive FUBC group had a larger proportion of multi-drug resistant organisms (MDRO) (21.9% vs. 10.4%, p < 0.001) with an odds ratio of 2.40 (95% CI = [1.53, 3.78]). In this group, those who received inadequate empiric antibiotics had a significantly higher percentage of repeat positive results (78.6% vs. 57.1%, p=0.033). In summary, patients with either an MDRO, a central line infection (vs. urinary tract infection), or the presence of a cardiac device (vs. no cardiac device present) had over twice the odds of positive FUBC than those without.

Conclusion :

Though the role of FUBC for gram-negative septicemia has been brought into question, our results show that the presence of central lines, cardiac devices, infections with MDRO organisms, or inadequate empiric antibiotics on admission were factors strongly correlated with subsequent positive FUBC. Therefore, we believe repeating blood cultures in this subset of patients requires further study and consideration.

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Nocardia bacteremia is almost always associated with immune compromise or an intravascular device: single center case series and systematic review of the literature

Eloise Williams, MBBS, BMedSci, MPHTM – Dr Eloise Williams, Austin Health

Adam Jenney, MBBS, FRACP, FRCPA, PhD – Dr Adam W. Jenney, Alfred Health

Denis Spelman, MBBS, FRACP, FRCPA, MPH – Dr Denis W. Spelman, Alfred Health

Background : Nocardia bacteremia is a rare but important phenomenon, with previous studies describing a 50% mortality rate. We undertake a single-center review and the largest systematic review of Nocardia bacteremia performed over the past 20 years.

Methods : A single-center review of cases of Nocardia bacteremia was performed using hospital microbiology records from January 1st 2010 to December 31st 2017. A systematic literature review was also performed to identify cases of Nocardia bacteremia described in the English language literature between January 1st 1999 and December 31st 2018 using the NCBI PubMed database and snowballing from citations of relevant publications.

Results : Single-center case series: Four cases of Nocardia bacteremia are described. Three patients had an intravascular device in situ prior to the onset of Nocardia bacteremia and three patients were immunocompromised; one patient had both risk factors.
Systematic literature review: A systematic review identified 50 publications that described 85 cases with sufficient patient data to be reviewed in detail. Including the 4 cases described in our institution, 89 cases of Nocardia bacteremia were included in the analysis. Median age was 57 years [interquartile range (IQR) 42-68] and 69% were male. Eighty-two percent of cases were immunocompromised and 38% had endovascular devices. Pulmonary infection was the most common concurrent site of clinical disease (66%), followed by central nervous system (25%), pleural (17%) disease and endocarditis (11%). Blood cultures were the only positive microbiological specimen that isolated Nocardia in 45% of cases. Median incubation time to blood culture positivity was 4 days [IQR 3-6]. 30-day all-cause mortality was 24% and overall all-cause mortality 42%.

Conclusion : Four new cases of Nocardia bacteremia are described. Isolation of Nocardia from blood cultures is rare but represents serious infection with high associated overall mortality. Nocardia bacteremia is most frequently identified in immunocompromised patients and those with intravascular devices.

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The Impact of Early Central Venous Catheter Removal in the Management of Enterococcus Central Line-Associated Bloodstream Infections

Hesham Awadh, MD – Infectious Disease Fellow, University of Texas Health Science Center at Houston/MD Anderson Cancer Center

Melissa Khalil, MD – Research Data Coordinator, The University of Texas MD Anderson Cancer Center

Anne-Marie Chaftari, MD – Associate Professor, The University of Texas MD Anderson Cancer Center

Johny Fares, MD – Postdoctoral Fellow, The University of Texas MD Anderson Cancer Center

Ying Jiang, MS – Research Statistical Analyst, MD Anderson Cancer Center

Rita Deeba, MD – Research Data Coordinator, The University of Texas MD Anderson Cancer Center

Shahnoor Ali, MD – Research Data Coordinator, The University of Texas MD Anderson Cancer Center

Ray Hachem, MD – Professor, MD Anderson Cancer Center

Issam Raad, MD – Professor and Chair, The University of Texas MD Anderson Cancer Center

Background :

There has been a rise in Enterococcus species Central Line-Associated Bloodstream Infections (CLABSI) ranking as the third overall causative organism according to the Center for Disease Control and Prevention (CDC) report issued in 2014. Central Venous Catheter (CVC) management including the need and timing of CVC removal is not well defined for enterococcus bacteremia (EB) in the 2009 Infectious Diseases Society of America (IDSA) management guidelines given the paucity of studies addressing CVC management. 

Methods :

We conducted a retrospective chart review on 543 patients diagnosed with EB between 2010 and 2018. We excluded patients without an indwelling CVC and those with mucosal barrier injury (MBI). We further evaluated 90 patients with EB that met the CDC definition for CLABSI without MBI or the IDSA definition for catheter-related bloodstream infections (CRBSI) and 90 patients with an indwelling CVC in place with documented non-CLABSI with another source. 

Results :

Early CVC removal (within 3 days of EB) was significantly higher in the CLABSI without MBI/CRBSI group compared to the non-CLABSI (43% vs 27%; p=0.02). Microbiological eradication associated with early CVC removal within 3 days of EB was significantly higher in the CLABSI without MBI/CRBSI group compared to the non-CLABSI (78% vs 48%; p=0.016). Complications were lower in the CLABSI without MBI/CRBSI compared to the non-CLABSI group (0% vs 18%; p=0.017). Defervescence, mortality (all cause and infection-related mortality) and relapse were similar in both groups. Within each group, outcome was similar irrespective of CVC management (removal within 3 days vs retention). 

Conclusion :

In cases of EB, early CVC removal within 3 days of bacteremia is associated with a favorable outcome in the CLABSI without MBI/CRBSI group compared to the non-CLABSI group.

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Cardiac Implantable Electronic Device-Related Infective Endocarditis (CIED-IE): Clinical Features and Outcomes of Patients with Definite IE Who Fufill Both Major Duke Criteria.

Siddhi Gupta, D.O. – Fellow, Wake Forest Baptist Medical Center

Thomas Wierzba, PhD – Professor, Wake Forest School of Medicine

James Peacock, Jr., M.D. – Physician, Wake Forest Baptist Medical Center

Larry Baddour, MD – Physician, Mayo Clinic College of Medicine

Muhammad Sohail, MD – Physician, Mayo Clinic

Katherine Le, MD – Physician, Mayo Clinic College of Medicine

Holenarasipur Vikram, MD – Infectious diseases program director, Mayo Clinic hospital, Phoenix, Arizona

José Miró, MD, PhD – Physician, Hospital Clinic-IDIBAPS, University of Barcelona

Jordan Prutkin, MD, MHS – Physician, University of Washington School of Medicine

Arnold Greenspon, MD – Physician, Thomas Jefferson University

Roger Carrillo, MD – Physician, Miller School of Medicine, University of Miami

Stephan Danik, MD – Physician, Massachusetts General Hospital

Christoph Naber, MD, PhD – Physician, University Hospital Essen

Elisabeth Blank, MD – Physician, Contilia Heart and Vascular Centre

Chi-Hong Tseng, PhD – Associate Professor, David Geffen School of Medicine, UCLA

Daniel Uslan, MD, MBA – Assistant Clinical Professor, UCLA

Background :

Cardiac implantable electronic device-related infective endocarditis (CIED-IE) comprises 10-57% of total CIED infections. Patients with definite CIED-IE who fulfill both major modified Duke criteria have not been well characterized.

Methods : Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective, multinational study of CIED infections were used to describe a subset of patients with CIED-IE who met both major Duke criteria for definite IE (bloodstream infection and intracardiac vegetations [VEG]).

Results :

Of 433 patients with CIED infection, 144 (33.3%) had definite CIED-IE. The median age was 68 years and 77.1% were male. Twelve (8.3%) had past CIED infection. Seventy-seven patients (53.5%) had permanent pacemakers, 38 (26.4%) had implantable cardioverter defibrillators, and 29 (20.1%) had combination devices. Median time following the last device procedure was 550 days. CIED-IE was early in 60 patients (41.7%) and late in 84 (58.3%).  Most patients presented with fever (77.8%) and sepsis (44.4%) with a median symptom duration of 7d.  On echocardiography, lead VEG were noted in 125 patients (86.8%) and valvular VEG in 54 patients (37.5%) with the tricuspid valve involved in 56.5%.  On the basis of VEG location, there were 90 patients (62.5%) with isolated lead-associated IE (LAE), 19 patients (13.2%) with isolated valve-associated IE (VAE), and 35 patients (24.3%) with both (LVAE).  All patients had positive blood cultures and 63/119 (52.9%) had positive lead cultures.  The predominant organism in blood was Staphylococcus aureus (42.4%), followed by coagulase-negative staphylococci (20.1%). CIED removal occurred in 131 patients (91%). There were 25 deaths during the index hospitalization and 34 total deaths (24.3%) by 6 months.  Mortality correlated with age > 75 (p=0.023) and sepsis on presentation (p=0.052).  Infecting organism, site of VEG, and device removal did not impact risk for death.

Conclusion :

Definite CIED-IE is relatively common.  The majority of patients tend to have late-onset infection and often present with sepsis.  S. aureus is the dominant organism causing definite CIED-IE.   Isolated LAE occurs in 63% of patients.  Older age and sepsis on admission are associated with higher mortality.

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Impact of Enterococcal Bacteremia on Clinical Outcomes in Patients with Liver Cirrhosis

Kady Phe, PharmD, BCPS – Clinical Pharmacist II – Infectious Diseases/Antimicrobial Stewardship, CHI St. Luke's Health - Baylor St. Luke's Medical Center

Isabel Won, PharmD – Pharmacy Practice Resident, CHI St. Luke's Health - Baylor St. Luke's Medical Center

Travis Carlson, PharmD – Postdoctoral Fellow, University of Houston College of Pharmacy

Hannah Russo, PharmD – Clinical Pharmacist II – Infectious Diseases/Antimicrobial Stewardship, CHI St. Luke's Health - Baylor St. Luke's Medical Center

Raymond Yau, PharmD, BCPS – Clinical Pharmacist II – Liver Transplant, CHI St. Luke's Health - Baylor St. Luke's Medical Center

Background : Patients with liver cirrhosis are at an increased risk for bacterial infections due to bacteria overgrowth and dysregulation of the intestinal barrier function. These infectious complications are associated with significant morbidity and mortality. Currently, there is a paucity of literature evaluating the clinical outcomes of patients with enterococcal bacteremia and cirrhosis. We hypothesized that patients with cirrhosis and subsequent enterococcal bacteremia would have a higher odds of mortality.

Methods : This was a retrospective, case-control study including adult patients (> 18 years) with liver cirrhosis and > 1 positive blood culture with Enterococcus species (ENT) admitted from June 2013 through August 2018. These cases were then matched with cirrhotic patients without enterococcal bacteremia (NO ENT) in a 1:1 ratio based on the Model for End-Stage Liver Disease (MELD) score. The primary endpoint was all-cause inpatient mortality. Multivariable logistic regression was used to control for other patient covariates.

Results : A total of 136 patients were identified during the study period (68 ENT and 68 NO ENT). The median length of stay was significantly longer in ENT patients (24.5 vs. 9 days, p < 0.001), while NO ENT patients were more likely to have renal dysfunction (55.9% vs. 83.8%, p < 0.001). All other baseline characteristics between the two groups were similar. Inpatient mortality was found to be significantly higher in ENT patients than NO ENT patients (51.5% vs. 29.4%, p = 0.009). In the multivariable analysis, risk factors found to be independently associated with mortality included enterococcal bacteremia (OR 3.96, 95% CI 1.61-9.73), MELD score (OR 1.11, 95% CI 1.05-1.19), and APACHE II score (OR 1.14, 95% CI 1.06-1.23).

Conclusion :

Enterococcal bacteremia, MELD score, and APACHE II score were found to be independent risk factors for all-cause inpatient mortality in patients with liver cirrhosis. Future studies are needed to elucidate how treatment choice and bacterial characteristics might also influence patient outcomes.

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Impact of Levofloxacin MIC on Outcomes with Levofloxacin Step-down Therapy in Enterobacteriaceae Bloodstream Infections

Melissa White, PharmD – Infectious Diseases Pharmacy Resident, Hospital of the University of Pennsylvania

Kerry Lenzi, PharmD – Pharmacy Resident, Hospital of the University of Pennsylvania

Lauren Dutcher, MD – Infectious Diseases Postdoctoral Fellow, University of Pennsylvania

Stephen Saw, PharmD – Clinical Pharmacy Specialist, Hospital of the University of Pennsylvania

Steven Morgan, PharmD, BCPS AQ-ID – Clinical Pharmacy Specialist, Hospital of the University of Pennsylvania

Shawn Binkley, BS, PharmD – Clinical Pharmacy Specialist, Infectious Diseases, Hospital of the University of Pennsylvania

Vasilios Athans, PharmD, BCPS, BCIDP – Clinical Pharmacy Specialist, Infectious Diseases, Hospital of the University of Pennsylvania

Christo Cimino, PharmD, BCPS, AAHIVP – Clinical Pharmacy Specialist - Infectious Diseases, Penn Presbyterian Medical Center

Kathleen Degnan, MD – Assistant Professor of Clinical Medicine, Hospital of the University of Pennsylvania

Keith Hamilton, MD – Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania

Background : The Clinical and Laboratory Standards Institute reduced the levofloxacin minimum inhibitory concentration (MIC) breakpoint from ≤ 2 mg/L to ≤ 0.5 mg/L for Enterobacteriaceae in 2019 guidelines. The reduction is based on Monte Carlo simulations for a levofloxacin dose of 750 mg daily. The aim of this study was to determine if there was a difference in clinical outcomes in the treatment of Enterobacteriaceae bacteremia with levofloxacin step-down therapy retrospectively comparing patients with isolates with low levofloxacin MICs (≤ 0.5 mg/L) to high MICs (1-2 mg/L).

Methods : This retrospective, two-center cohort study included patients ≥ 18 years of age with a monomicrobial Enterobacteriaceae bacteremia with a levofloxacin MIC ≤ 2 mg/L from March 2017 through December 2018. Patients had to have received treatment with ≥ 3 days of levofloxacin step-down therapy, initial intravenous therapy with an agent active against the isolated organism, and total duration not exceeding 16 days from first negative blood culture. A subset of patients whose isolates had low levofloxacin MICs were randomly selected for comparison to all patients with high levofloxacin MICs in a 3:1 ratio. The primary outcome was a composite endpoint of recurrence and mortality within 30 days of completion of the antibiotic course. Secondary outcomes included post-culture length of stay (LOS) and 30-day readmission rate.

Results : Thirty-three patients with high MIC and 99 with low MIC were included. Urinary source was predominant and occurred in 44% of patients, and Escherichia coli was the infecting organism in 48%. Over 80% of patients experienced source resolution or control. The composite endpoint occurred in 8.1% of the low MIC group and 9.1% of the high MIC group (p = 0.856). Median LOS was 4.9 days (IQR 3.7 - 8.0) in the low MIC group and 4.3 days (IQR 3.2 - 6.8) in the high MIC group (p = 0.384), and readmission rate was 17.2% in the low MIC group and 15.2% in the high MIC group (p = 0.787).

Conclusion : There was no between-group difference in the primary outcome of recurrence and mortality, with a low overall event rate and short LOS post-culture. These results suggest that levofloxacin effectiveness may be sustained in patients with MICs of 1 or 2 despite levofloxacin not meeting susceptibility criteria by new definitions.

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The Clinical Impact of 16S rRNA Bacterial Sequencing in Infective Endocarditis

Sami El-Dalati, MD – University of Michigan, Fellow

Sandro Cinti, MD – Professor, University of Michigan

Anna Owczarczyk, MD, PhD – House Officer, University of Michigan

Jamie Riddell, IV, MD – Professor, University of Michigan

Christopher Fagan, MD – House Officer, University of Michigan

Rishi Chanderraj, MD – Clinical Instructor, University of Michigan

Shinichi Fukuhara, MD – Assistant Professor, University of Michigan Frankel Cardiovascular Center

Background :

Cases of possible and/or culture negative endocarditis continue to be a diagnostic challenge.  Performing bacterial 16S ribosomal RNA polymerase chain reaction (rRNA PCR) sequencing on cardiac valves now allows providers to make microbiologic diagnoses that were previously unobtainable (sensitivity 66-80.5%).  However, few publications address how the PCR results impact clinical management in endocarditis patients.

Methods :

Between July 1st, 2014 and December 31st, 2018, the results of all 16S rRNA PCR tests collected from cardiac valves at the University of Michigan were reviewed.  Samples were sent to the University of Washington for sequencing.  Each chart was then reviewed by two independent ID physicians to determine whether patients’ medical plans were impacted by the PCR results.

Results :

41 patients were identified with associated 16S rRNA PCR testing from cardiac valves.  16 cases met Duke Criteria for definite endocarditis, 22 for possible and 3 were rejected endocarditis.  Overall, 18 (43.9%) samples were positive.  Of these, 10 patients had concordant positive blood cultures.  In 8 patients a previously unsuspected organism was identified.  24 out of 41 patients were considered to have culture negative endocarditis with 10/24 (41.7%) who had positive PCR results.   22 patients were noted to have operative findings consistent with infection with 16 (72.7%) having corresponding positive PCR results.  4/41 (9.8%) patients had their management plans changed based solely on the PCR findings.    In 23/41 (56.1%) cases the PCR result was never referenced by any medical provider in the electronic medical record.  There were 7 (17.1%) cases where patients received 6 weeks of antibiotics despite presenting with possible culture negative endocarditis, non-infectious operative findings and negative valve PCRs which were not reviewed.

Conclusion :

16S rRNA PCR sequencing is a useful tool for obtaining a microbiologic diagnosis in cases of possible or culture-negative endocarditis.  The test has significant potential to impact individual patient care and in a subset of cases may be used to de-escalate antibiotic therapy.  However, testing delays and cumbersome resulting methods impede bacterial sequencing from reaching its full potential as a diagnostic modality.

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Cascade of Care for Opioid Use Disorder in Patients with Infective Endocarditis

Carlos Saldana, MD – Resident, Cleveland Clinic Foundation

Gabriella Bal – Ms, Cleveland Clinic

Nabin Shrestha, MD, MPH – Staff Physician, Cleveland Clinic

Kristin Englund, MD – Staff Physician, Cleveland Clinic

Steven Gordon, MD – Chairman Department of Infectious Diseases@Steven, Cleveland Clinic Foundation

Background :

The term “Cascade of Care” has been used to analyze care delivered by a health system for conditions such as HIV, hepatitis C, tuberculosis, and diabetes. It outlines sequential steps required to reach a specific outcome (i.e. viral suppression in the case of HIV). This allows to estimate the proportion of patients achieving each step and to identify gaps in care.

Medication-assisted treatment (MAT) is integral in the treatment of patients with infective endocarditis (IE) and opioid use disorder (OUD). We propose a Cascade of Care aiming to identify fundamental milestones in the management of these patients.

Methods :

A retrospective cohort study examined patients with IE in the setting of OUD hospitalized between 7/1/2007 and 1/1/2015 to the Cleveland Clinic. We identified 4 key steps along the treatment cascade of these patients and estimated the proportion of patients: 1) evaluated by an addiction treatment service, 2) prescribed MAT while in-patient, 3) prescribed MAT at discharge, and 4) continued MAT at least 90 days after discharge.

Results :

Of 273 patients with IE in the setting of OUD, 134 (49%) were evaluated by an addiction treatment service; 45 (17%) were prescribed MAT while in-patient; only 22 (8%) were prescribed MAT at discharge. At 90 days following discharge, there was evidence of continuing MAT for all 22 patients (8%).

Conclusion :

Describing the process of addiction treatment for patients with IE and OUD in the format of a cascade of care provides a powerful quantitative method to identify gaps in care and can be used as a resource to implement interventions to address losses. We found only 8% of these patients continued MAT in the community after discharge. This study provides an estimate of how compromised the potential benefits from medical and surgical treatment for IE are by the lack of an effective approach to OUD after hospital discharge.

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Novel treatment approach for Left Ventricular Assist Device related infections

Yunus Yalcin, BSc – BSc, Erasmus Medical Center

Nelianne Verkaik, MD, PhD – Dr., Erasmus Medical Center

Hannelore Bax, MD, PhD – Dr., Erasmus Medical Center

Peter Croughs, MD, PhD – Dr., Erasmus Medical Center

Ad Bogers, MD, PhD – Dr., Erasmus Medical Center

Kadir Caliskan, MD, PhD – Dr., Erasmus Medical Center

Background :

Left ventricular assist device (LVAD) implantation has become an effective treatment option for patients with severe heart failure. However, infections remain a substantial risk. Therefore, the aim of this study is to gain insight in the incidence and outcome of LVAD infections in our center and develop an up-to-date flowchart for the management of LVAD related infections.

Methods :

A retrospective study was performed which included all patients with a LVAD implanted between 2006 until 2019, along with a rigorous review of the current literature. Clinical records and microbiological laboratory results of all patients were reviewed. In view of local infectious complications, a flowchart was developed for the contemporary management of LVAD related infections (Figure 1). 

Results :

Overall, 106 patients (median age 54 years [IQR 47-60], 78% male) were included, of whom 92 (87%) as bridge-to-transplantation/decision and 14 (13%) as destination therapy. LVAD related infections occurred in n=30 (28%) of the patients. Median time until first infection was 308 days [IQR 115-528], and median duration of hospital stay was 16 days [IQR 4-29]. Eighty percent of LVAD related infections were driveline related. The most common causative pathogen was Staphylococcus aureus, which was present in almost half of the cases (40%). Patients who experienced infections were younger (46 [IQR 37-57] vs 56 [IQR 52-62]; p<0.001).The survival rate at 3 years was 76% in the infected versus 94% not infected patients; p=0.037). A secondary infection occurred in 10 patients (33%). At 3 years of follow-up, 31 patients were successfully transplanted. Six patients with deep S. aureus driveline infections were treated according to the standardized protocol of whom 2 with suppressive therapy by cephalexin, with clinical success so far.

Conclusion :

LVAD infections occur frequently and lead to prolonged periods of hospital admissions and death. The lack of standardized treatment regimens complicates the treatment of LVAD related infections. A comprehensive flowchart to treat future LVAD related infections in a protocolized fashion was developed, based on our single center experience. While the preliminary results look promising, more follow-up time of the treated patients is needed.

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Adequacy of Commonly Prescribed Antimicrobials for Empiric Coverage of Gram-Negative Bacterial Pathogens Recovered from the Bloodstream of Patients Attending Emergency Rooms in Canada: Analysis of Data from the CANWARD Study, 2007 to 2018

Andrew Walkty, MD – Medical Microbiologist, Shared Health

Heather Adam, PhD – Clinical Microbiologist, Shared Health

Melanie Baxter, MSc – Research Co-ordinator, University of Manitoba

Amina Henni, MD – Physician, Max Rady Colleg of Medicine, University of Manitoba

Philippe Lagace-Wiens, MD – Medical Microbiologist, Shared Health

James Karlowsky, PhD – Clinical Microbiologist, Shared Health

George Zhanel, PhD – Professor, Max Rady Colleg of Medicine, University of Manitoba

Background :

Inadequate empiric antimicrobial therapy for Gram-negative bacteremia is associated with adverse clinical outcomes.  The purpose of this study was to evaluate the proportion of Gram-negative bacterial isolates recovered from the bloodstream of patients attending Canadian emergency rooms (ERs) that remain susceptible to commonly prescribed antimicrobials.

Methods :

Annually from 2007 to 2018, sentinel hospitals across Canada collected bloodstream isolates from patients attending ERs as part of the CANWARD Study.  Susceptibility testing was performed using broth microdilution as described by CLSI (data analysis limited to Gram-negative bacteria in the top 10 pathogens), with current CLSI breakpoints applied.  Extended-spectrum beta-lactamase (ESBL)-producing isolates were confirmed using the CLSI disk diffusion method. 

Results :

Gram-negative bacteria among the top 10 bloodstream pathogens for patients seen at ERs across Canada were: Escherichia coli (n = 2414), Klebsiella pneumoniae (n = 573), Pseudomonas aeruginosa (n = 211), Proteus mirabilis (n = 119), and Enterobacter cloacae (n = 114).  Aggregate susceptibility of these isolates to common antimicrobials was as follows (% susceptible [S]): meropenem 99.4% S, piperacillin-tazobactam 98.5% S, gentamicin 93.3% S, ceftriaxone 88.1% S, ciprofloxacin 81.4% S, TMP-SMX 73.5% S.  The most active antimicrobials evaluated versus E. coli were meropenem (100% S), piperacillin-tazobactam (98.8% S), and ceftriaxone (93.3% S).  Ceftriaxone susceptibility among E. coli isolates declined from 95.4% in 2007 to 89.8% in 2018.  The average proportion of E. coli isolates that harbored an ESBL enzyme increased from 3.4% in the first three study years to 8.4% in the last three study years.  The most active antimicrobials evaluated versus K. pneumoniae isolates were meropenem (99.7% S), piperacillin-tazobactam (98.8% S), gentamicin (97.7% S), and ceftriaxone (96.9% S).

Conclusion :

The most consistently active antimicrobials for empiric treatment of patients at Canadian ERs with Gram-negative bacteremia are meropenem and piperacillin-tazobactam.  Ceftriaxone susceptibility among E. coli has declined over the last 12 years, mostly related to an increase in ESBL-producing isolates. 

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Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Patients with Bloodstream Infections in United States Medical Centers (2017-2018)

Cecilia Carvalhaes, MD, PhD – Associate Director, JMI Laboratories, Inc.

Mariana Castanheira, PhD – COO, JMI Laboratories

Rodrigo Mendes, PhD – Director, JMI Laboratories

Helio Sader, MD, PhD – Senior Director, JMI Laboratories

Background :

We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in United States (US) hospitals.

Methods :

A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017-2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-lactamase screening was performed by whole genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype).

Results :

The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime-avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane-tazobactam (C-T) and piperacillin-tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2-98.9%S; Table), with limited activity against ECL (81.9-83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n=333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA.

Conclusion :

CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals.

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Clinical Presentation and Molecular Epidemiology Characterization of Invasive GBS Infection in Nara, Japan from 2007 to 2016

nobuyasu hirai, 4th year degree – medical student, Nara Medical University

Kei Kasahara, PhD – Associate Professor, Nara Medical University

Yoshihiko Ogawa, 5th year degree – ID, Nara Medical University

Yuki Suzuki, 4th year degree – assistant professor, Nara Medical University

Naokuni Hishiya, 4th year degree – medical student, Nara Medical University

Ryuichi Nakano, PhD – Senior Lecturer, Nara Medical University

Hisakazu Yano, MD, PhD – Professor, Nara Medical University

Masahide Yoshikawa, PhD – Professor, Nara Medical University

Keiichi Mikasa, MD, PhD – Professor, Nara Medical University

Background : Streptococcus agalactiae (GBS), a leading cause of neonatal infections, also occurs as an invasive infection in elderly people. The aim of this study was to evaluate the clinical aspect of invasive infections and the phenotypic and genetic diversity of GBS isolates to develop better antibiotics treatment and curb the increasing rate of antibiotic resistance in Nara, Japan.

Methods : GBS strains sequentially collected from blood and cerebrospinal fluid cultures between 2007 and 2016 were identified and evaluated for capsular types, multilocus sequence typing (MLST), antibiotic susceptibility, resistant gene and pulsed-field gel electrophoresis (PFGE). Clinical characteristics were retrospectively collected.

Results : A total of 42 GBS isolates (12 from children and 30 from adults) were collected. In adults, common underlying conditions were malignancy and diabetes, and primary bacteremia was the most common source of infection. In children, 6 were early-onset diseases, 4 were late-onset diseases, and 2 were school children. Overall, the mortality rate was 0% in children and 17% in adults. The serotypes and main clonal complex are summarized in Table 1. Minimum inhibitory concentrations of the antibiotics were also determined (Table 2). The serotypes and resistant genes are shown in Table 3. PFGE revealed serotypes V and VI belonging to ST1, and serotype III belonging to ST335 were highly identical.

Conclusion : In clinical aspects, neonates with early-onset diseases experienced certain disorders during the perinatal period. In adults, serotype Ib, which tends to exhibit levofloxacin resistance, was the most common, followed by serotypes V and VI belonging to ST1; however, they were not observed in children. Contrastingly, serotype III belonging to ST335, which tends to exhibit macrolide resistance, was mainly observed in children. Quinolone among adults and macrolide among the younger generation are widely used as oral antibiotics in Japan. A tendency to use antibiotics affects bacterial flora and induces selectivity of specific clones, thereby causing diseases in the local community. Continuous surveillance is warranted in local areas for appropriate antibiotics treatment and prevent increasing antibiotic resistant isolates.

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Duration of Therapy for the Treatment of Gram-Negative Bloodstream Infections

Stephanie Shulder, PharmD, BCIDP – Infectious Diseases Clinical Pharmacy Specialist, University of Rochester Medical Center

Matthew O'Connell, PharmD – PGY-1 Pharmacy Resident, University of Rochester Medical Center

Kaitlyn Agedal, PharmD Candidate 2020 – Pharmacy Student, St. John Fisher College Wegmans School of Pharmacy

Kelly Conn, PhD, MPH – Assistant Professor, St. John Fisher College, Wegmans School of Pharmacy

Kelly Pillinger, PharmD, BCIDP – Infectious Diseases Clinical Pharmacist, University of Rochester Medical Center

Background : While current guidelines suggest a total treatment duration of 7 to 14 days for gram-negative bloodstream infections (GN-BSI), there is mounting evidence to suggest that shorter durations may be sufficient. This study compared treatment outcomes of patients who received short duration therapy (6-10 days) with those who received long durations (11-15 days).

Methods :

This was a retrospective study of adult patients who grew an aerobic gram-negative organism from a blood culture while admitted at Strong Memorial Hospital between May 2016 and May 2018. The primary outcome was a composite of mortality and relapsed GN-BSI with the same organism within 90 days of index culture. Secondary outcomes included clinical resolution at end of therapy (EOT), length of stay (LOS), 30-day readmission rate, Clostridoides difficile infection (CDI), development of recurrent GN-BSI resistant to prior antibiotic therapy, and development of multi-drug resistant (MDR) GN-BSI within 90 days. Appropriate therapy was defined as an antibiotic with confirmed in vitro susceptibility that was either parenteral or a highly bioavailable oral antibiotic (fluoroquinolones or sulfamethoxazole-trimethoprim).

Results : Of 600 patients screened, 116 were included in the long duration group and 34 patients in the short duration group.  The majority of patients had a urinary source of infection (59.3%). The primary composite outcome occurred in 11.8% of the short duration group compared to 10.3% in the long (P > 0.999). There was no difference in clinical resolution at EOT, LOS, or rates of CDI, MDR GN-BSI, recurrent GN-BSI resistant to prior therapy, or 30-day readmission. Patients in the long duration group were discharged with longer appropriate outpatient courses (8 days vs. 0.5 days, P < 0.001), which remained significant when including lower bioavailability agents (e.g. oral beta lactams) (8 days vs. 5 days, P < 0.001).

Conclusion : There was no difference in clinical outcomes between the long and short duration therapy for treatment of GN-BSI. This study may support shorter treatment durations for uncomplicated GN-BSI, but should be interpreted cautiously given the smaller sample size.

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