bluuebunny/crossref_metadata_2025 huggingface dataset:
114. Chorioretinal Lesions in Persons Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections
Authors: Greven Margaret A , Weinstein Jessica , Tsamis Kathy , Ayres Philippe F , Barnes Erin W , Peacock James E
Published: October 2019

Background

Eye infection is one of the many potential sites of infection in persons who inject drugs (PWID). The purpose of this study was to determine the prevalence of chorioretinal (CR) lesions, identify causative organisms, and correlate symptoms with ophthalmic involvement in PWID hospitalized with bloodstream infection (BSI) and/or related metastatic foci of infection (MFI).

Methods

Actively using PWID 18 years or older admitted to Wake Forest Baptist Med Ctr with documented BSI or MFI related to injection drug use (IDU) were prospectively enrolled after providing informed consent. All patients, whether or not they had eye symptoms, received a dilated retinal examination as soon as feasible after admission. Ocular symptoms, visual acuity, and ocular examination findings were recorded and fundus photos were obtained as indicated. Patients could be re-enrolled if re-admitted with a different infection.

Results

Fifty-three PWID with 55 episodes of disseminated infection related to IDU underwent ophthalmic exams at a median of 7 days post-admission. Mean age was 33.4 years and 51% were female. Twenty (38%) patients had HCV viremia but none had active HIV infection. Heroin was the injection drug of choice in 55% of patients. Of the 55 episodes of systemic infection, 33 were classified as infective endocarditis (IE), 6 were BSI only, 10 were BSI with MFI, and 5 were MFI without active BSI. Nine (17%) patients had CR involvement on examination but only 33% (3/9) were symptomatic. Of those with ocular involvement, 1 had fungal endophthalmitis due to Candida albicans. Single or multifocal subretinal infiltrates were found in 5/9 patients (MSSA 2, MRSA 2, H. parainfluenzae 1), 2/9 had cotton wool spots (S. mitis 1, MRSA 1), and 7/9 had intraretinal or white-centered hemorrhages (MSSA 3, MRSA 2, S. mitis 1, H. parainfluenzae 1). Of the 9 patients with CR lesions, 7 had IE. Interestingly, 3.8% (3/53) had old multifocal CR scars, possibly related to prior disseminated infection.

Conclusion

PWID admitted with BSI or MFI may have ophthalmic involvement even in the absence of ocular symptoms, especially in the setting of IE. Further study is needed to characterize the epidemiology of these infections, to identify risk factors for ocular involvement, and to optimize diagnosis and management.

Disclosures

All authors: No reported disclosures.
2213. Etiology of Community-Acquired Pneumonia (CAP) in Hospitalized Native American Adults
Authors: Hammitt Laura , Driscoll Amanda , Weatherholtz Robert , Reid Raymond , Colelay Janene , Grant Lindsay , VanDeRiet Daniel , Alexander-Parrish Ronika , Pride Michael W , McLaughlin John M , Gessner Bradford D , Isturiz Raul E , Santosham Mathuram , O’Brien Katherine
Published: October 2019

Background

Native Americans experience a high burden of community-acquired pneumonia (CAP). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced for adults ≥65yrs in 2014. Data on CAP etiology can guide prevention and treatment.

Methods

We enrolled adults hospitalized with CAP and age-group-matched non-hospitalized controls on Navajo and White Mountain Apache tribal lands. Nasopharyngeal/oropharyngeal (NP/OP) swabs from cases and controls were tested by multiplex PCR for respiratory pathogens. Urine from cases and controls was tested for pneumococcus (Sp) by conventional (BinaxNOW) and serotype-specific urine antigen detection (UAD) for 24 serotypes (PCV13 types plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F). Blood culture and chest radiographs (CXRs) were obtained from cases at the provider’s discretion. Radiographic pneumonia was determined by clinical interpretation of CXRs.

Results

From March 2016 to March 2018, we enrolled 580 CAP cases with CXR confirmation and 411 controls. Positive blood culture was identified in 42/483 (9%), of which 29 (69%) were Sp. Sp was detected in 164/572 (29%) cases (table). Of 125 cases with serotype information available, serotypes 3 (n = 35; 28%) 8 (n = 19; 15%) and 20 (n = 15; 12%) were the most common. Among 53 Sp cases aged ≥65 years, 26 (49%) were PCV13-type. Compared with blood culture, UAD was 100% sensitive and 100% concordant (n = 24). Viruses were detected by NP/OP PCR in 43% of CAP cases and 18% of controls. Influenza A, parainfluenza type 3, rhinovirus, and RSV were statistically significantly associated with case status. Among 263 cases in whom all diagnostic tests were collected, 63% had a pathogen detected: bacteria alone in 19%, viruses alone in 23%, and both bacterial and viral infection in 22%. Bacterial causes outnumbered viral causes when adjusting for virus detection in the control population.

Conclusion

Pneumococci were the most common etiology identified among Native American adults with CAP. UAD improved detection of pneumococcal CAP. Respiratory viruses also contributed substantially to CAP burden. Broader prevention strategies, including new vaccines, are required to prevent viral pneumonia and pneumococcal pneumonia caused by serotypes not contained in currently-available vaccines.

Disclosures

All authors: No reported disclosures.
2215. Diarrheal Illness as a Risk Factor for Subsequent Respiratory Infection Among Women and Infants in Nepal
Authors: Newman Kira L , Gustafson Kathryn , Englund Janet A , Khatry Subarna , LeClerq Stephen , Tielsch James , Katz Joanne , Chu Helen Y
Published: October 2019

Background

Globally, diarrheal and respiratory infections are responsible for nearly one-quarter of deaths in children under 5 years old. Historically these diseases have been studied separately; recent evidence suggests that preceding diarrheal disease may be a risk factor for subsequent respiratory illness. We sought to identify whether diarrhea was associated with subsequent respiratory illness in adult women and infants in Nepal.

Methods

We used data from a community-based, prospective randomized trial of maternal influenza immunization of pregnant women and their infants conducted in rural Nepal from 2011 to 2014. Diarrhea episodes were defined as at least three self-reported watery bowel movements per day for one or more days. Respiratory illness episodes were defined as the presence of fever with an additional respiratory symptom. Diarrhea and respiratory illness episodes were identified through longitudinal household-based weekly symptom surveillance. A case-crossover design was used to determine whether risk of respiratory infection was increased in the 30 days following a diarrhea episode compared with the 30 days prior.

Results

Of 3,693 women in the study and their 3,646 infants, 525 (14.2%) women experienced one or more episodes of diarrhea during pregnancy, 226 (9.4%) women experienced one or more episodes of diarrhea after pregnancy, and 342 (9.4%) infants had one or more episodes of diarrhea. The incidence of respiratory episodes during the exposure and control periods was approximately 2–5% in adults and 8–10% in infants. Preceding diarrhea was not significantly associated with respiratory infection in adult women or infants. There was a slight trend toward greater incidence of diarrhea during the exposure period among infants (Figure 1), but it was not statistically significant. These results held after a sensitivity analysis limiting follow-up time to 15 days before and after diarrhea episode.

Conclusion

In this study of pregnant and postpartum women and their infants in Nepal, diarrheal illness was not a significant risk factor for subsequent respiratory illness.

Disclosures

All authors: No reported disclosures.
2221. Chlamydia pneumoniae (Cpn) Induces IFN-γ Responses in Peripheral Blood Mononuclear Cells (PBMC) from Pediatric and Adult Asthma Patients: Effects of Age and Inhaled Corticosteroid Use
Authors: Szigeti Aviva , Hammerschlag Margaret , Weaver Diana , Smith-Norowitz Tamar , Kohlhoff Stephan
Published: October 2019

Background

Chlamydia pneumoniae (Cpn) is unique in its ability to cause chronic infections, potentially triggering asthma exacerbations as well as subsequent asthma development. Th1-mediated immunity and IFN-γ are critical for clearing chlamydial infections. Persistent or recent Cpn infection may be identified in vitro by detecting T-helper cytokine IFN-γ produced by peripheral blood mononuclear cells (PBMC) stimulated by Cpn. Inhaled corticosteroids (ICS) may have an inhibitory effect on IFN-γ. Prior studies have shown increased Th2 responses upon in vitro Cpn stimulation with increased age. Our aim was to determine whether age and inhaled corticosteroid (ICS) use affect Cpn-induced PBMC produced IFN-γ levels.

Methods

Pediatric and adult subjects with (n = 23) and without (n = 10) asthma were enrolled. PBMC obtained from all subjects were stimulated with Cpn (MOI = 0.1 x48h) in vitro. IFN-γ levels in culture supernatants were determined by ELISA and reported as pg/mL. Nasopharyngeal (NP) swabs were tested for Cpn using Real-Time PCR. Statistical analysis for continuous variables was performed using the Mann–Whitney U test.

Results

None of the subjects were positive for Cpn by PCR on NP swab. Levels of IFN-γ produced by PBMC stimulated by Cpn were similar between asthmatic vs. control subjects (41.7 vs. 68.8, respectively; P = 0.72) and between pediatric and adult subjects with asthma (IFN-γ 54 vs. 20.1 respectively, P = 0.95). Pediatric subjects with asthma who received ICS had lower IFN-γ levels than those who did not (median IFN-γ 25.5 vs. 209; P = 0.003).

Conclusion

Our finding of lower IFN-γ levels among asthma patients on ICS compared with those not on ICS suggests that ICS use may dampen the systemic inflammatory response. While we did not find a statistically significant difference between pediatric and adult age groups in this pilot study, there was a trend to higher Cpn-induced IFN-γ levels among younger pediatric subjects. Future prospective studies should further define predictors of diminished IFN-γ responses in patients with asthma.

Disclosures

All authors: No reported disclosures.
2225. Are Fluoroquinolones or Macrolides Better for Treating Legionella Pneumonia? A Systematic Review and Meta-Analysis
Authors: Jasper Annie S , Musuuza Jackson S , Stevens Vanessa W , Gamage Shantini D , Safdar Nasia
Published: October 2019

Background

Reported cases of Legionella pneumonia continue to rise in the United States; with mortality rates of 9–25%. The Infectious Disease Society of America recommends either a fluoroquinolone or azithromycin as the first-line treatment for legionellosis. While treatment of Legionella pneumonia improves outcome, it is uncertain as to which antibiotic offers optimal clinical outcomes. We undertook a systematic review and meta-analysis to compare the effectiveness of fluoroquinolone vs. macrolide monotherapy in Legionella pneumonia.

Methods

We conducted a systematic search of literature in multiple databases through April 2019. Studies on patients diagnosed with Legionella pneumonia and treated with either antibiotic of interest were included. Mortality was used as the primary outcome to compare fluoroquinolones and macrolides. Secondary outcomes were clinical cure, time to apyrexia, length of hospital stay (LOS), and the occurrence of complications. We estimated pooled odd ratios to compare the odds of death, clinical cure, and complications. The standard mean difference was estimated for LOS and time to apyrexia. We used a random-effects model and estimated heterogeneity using the I2 statistic. We also analyzed the risk of mortality by setting, i.e., intensive care unit (ICU) vs. non-ICU studies.

Results

Of the 1,583 abstracts reviewed, 20 studies with a total of 3,656 patients met inclusion criteria. The mean age of the population was 60.9 years and 68.5% were men. The mortality rate for patients treated with fluoroquinolones was 7% (102/1454) and 7.7% (125/1615) among those treated with macrolides. The overall pooled odds ratio (OR) assessing mortality risk for patients treated with fluoroquinolones vs. macrolides was 0.95 (95% CI 0.71–1.27, I2 = 0%, p = 0.54). Odds ratios for subgroup analyses were: ICU studies (OR = 1.27, 95% CI: 0.18–9.08, I2 = 45%, p = 0.158); non-ICU studies (OR = 0.96, 95% CI: 0.71–1.32, I2 = 0%, p = 0.616) (figure). Clinical cure, time to apyrexia, LOS, and the occurrence of complications did not differ between fluoroquinolones and macrolides.

Conclusion

Fluoroquinolones and macrolides were found to have similar effectiveness in treatment of Legionella pneumonia for mortality outcomes. However, insufficient data for secondary outcomes was a limitation of this analysis.

Disclosures

All authors: No reported disclosures.
2229. Relative Bioavailability of a Single Oral Dose of SUBA-Itraconazole 65 mg Capsule Compared with Conventional Itraconazole 100 mg Capsule Administered Under Fasted and Fed Conditions in Healthy Adult Volunteers
Authors: Mudge Stuart , Lewis Phoebe , Burnett Bruce P
Published: October 2019

Background

Conventional itraconazole (CI) absorption from capsules even under fed conditions is suboptimal (~55%), let alone when fasted. SUBA-itraconazole (SI) is ~1.8x’s more bioavailable than CI at steady-state in a fed condition. There are, however, no data comparing these formulations under a fasted state. A single-dose PK study was performed comparing bioavailability of 65mg SI to 100mg CI under fasted or fed conditions.

Methods

This was an open-label, single-dose, randomized, four-period, four-treatment, four-sequence, crossover bioequivalence study under fasted and fed conditions in healthy adults. Subjects were administered a single dose of SI (1 × 65 mg) and CI (1 × 100 mg). Under fasted condition, subjects were administered SI or CI following an overnight fast of at least 10 hours. Subjects under fed condition were administered SI or CI after 30 minutes of consuming a standardized high fat breakfast preceded by an overnight fast of at least 10 hours. After dosing, all subjects fasted for at least 4 hours post-dose in all periods. Blood samples were collected prior to dosing and then from 1 to 120 hours. Analysis of itraconazole (IZ) and hydoxyitraconazole (HIZ) serum levels was by least-squares-geometric means of PK parameters.

Results

Under fasted condition, Cmax and AUCtau of IZ for SI were substantially higher compared with CI (Table, Figure 1). Under fed conditions, however, the Cmax and AUCtau of IZ for SI was 20% and 10% lower, respectively (table, Figure 2). Similar results were found for HIZ. The Tmax for IZ and HIZ of SI and CI were similar under a fasted condition but extended by over 2 hours for SI vs. CI under fed conditions. Study drugs were well-tolerated under fasted and fed conditions. All TEAEs were mild and resolved at the end of the study. Fifty of 52 subjects enrolled completed the study. Two subjects did not complete the study due to not being able to finish a high fat meal and noncompliance. No SAEs were reported.

Conclusion

Total and peak IZ/HIZ exposure was substantially higher for SI under fasted conditions compared with CI, but slightly lower under fed conditions with similar safety profiles. This study demonstrates the unique nature of the SI formulation compared with CI under fasted conditions and may lead to less variability if patients are not adherent to dietary requirements when taking itraconazole.

Disclosures

All authors: No reported disclosures.
2230. Analysis of the Microbiological Data from the Delafloxacin (DLX) Phase 3 Community-acquired Bacterial Pneumonia (CABP) Trial
Authors: McCurdy Sandra , Keedy Kara , Lawrence Laura , Sheets Amanda , Quintas Megan
Published: October 2019

Background

DLX is a novel fluoroquinolone (FQ) antibiotic with Gram-positive/MRSA, Gram-negative and atypical activity. It offers IV and oral treatment with no QT restrictions. In a Phase 3 study in CABP patients, DLX was non-inferior to moxifloxacin (MOX) in the primary endpoint, early clinical response at 96 ± 24 hours (88.9 vs. 89.0; 95% CI: −4.4, 4.1) in the intent-to-treat (ITT) population. A detailed microbiological analysis was conducted.

Methods

CABP pathogens were identified by culture/non-culture methods. Pathogens identified by non-culture methods included Streptococcus pneumoniae (Sp; culture, urinary antigen [UA], nasopharyngeal [NP] swab lytA PCR), Legionella pneumophila (Lp) (culture, UA, serology), Mycoplasma pneumoniae (Mp; culture, serology), and Chlamydia pneumoniae (Cp; serology). All other pathogens were identified using culture only. For Sp cultured from NP, a concomitant lytA PCR value of ≥ 1000 gene copies/mL was required. All isolates underwent susceptibility testing, and a subset of isolates underwent molecular or phenotypic characterization including whole-genome sequencing for FQ resistance mechanisms, PCR for PVL/mecA genes (S. aureus), β-lactamases (Haemophilus/Moraxella spp), and serotyping (Sp).

Results

Included in submitted image.

Conclusion

DLX demonstrated potent in vitro and clinical activity against CABP pathogens, including Sp [MRSP, MDRSP, PRSP], MRSA, Haemophilus species, Enterobacteriaceae, P. aeruginosa, and the atypical pathogens Cp, Mp, and Lp.

Disclosures

All authors: No reported disclosures.
116. Risk Factors and Clinical Outcomes of Carbapenem Non-Susceptible Gram-Negative Bacteremia in Patients with Acute Myelogenous Leukemia
Authors: Hoon Shin Dong , Il Jun Kang , Mi Moon Song , Beom Park Wan , Hwan Bang Ji , Suk Kim Eu , Won Park Sang , Bin Kim Hong , Kim Nam-Joong , Kyung Kang Chang , Oh Myoung-don
Published: October 2019

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 the 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.

Disclosures

All authors: No reported disclosures.
2242. Use of a Procalcitonin Assay in Hospitalized Patients for CHF Reduced Subsequent Use of Antibiotics
Authors: Majeed Irfan , Levine Zachary , Szpunar Susan M
Published: October 2019

Background

Procalcitonin (PCT) is a biomarker that rises in bacterial infections and is being increasingly used to support a diagnosis of bacterial pneumonia. In addition, it may be used in cases in which the diagnosis is not clear such as in patients with congestive heart failure (CHF), which may mimic the signs and symptoms of bacterial pneumonia. The PCT assay was implemented at our institution to reduce unnecessary antimicrobial use when evaluating patients for suspected pneumonia.

Methods

We performed a retrospective analysis of all patients with a discharge diagnosis of CHF, admitted in a 6-month period, to a large community teaching hospital. Patients with documented pneumonia were excluded. Data were collected on demographics, comorbidities to calculate the Charlson Weighted Index of Comorbidity (CWIC) score, clinical and laboratory information, PCT results (if collected), whether antimicrobials were used, and if so, duration of therapy. Data were analyzed using the Mann–Whitney U test.

Results

We reviewed 299 charts, with 198 (66.2%) included for analysis. The mean age was 70.4 ± 15.0 years, 53% female and 49.5% black. PCT testing was done in 72 (36%) patients; 117 (59%) had antimicrobials given in the emergency department (ED). If the PCT was performed, patients were more likely to receive antibiotics in the ED (79.2% vs. 47.6%, P < 0.0001). Patients who had a PCT drawn were less likely to have antibiotics continued after discharge from the ED (27.6% vs. 73.3%, P < 0.0001). The median duration of antimicrobials was shorter in patients who had a PCT level drawn than those who did not, 1 day (range 0.5–14) vs. 3 days (0.5–61), P < 0.0001. The duration of antimicrobials also tended to be shorter in patients with PCT levels ≤ 0.25 compared with those with levels >0.25, 0.5 days (0.5–12) vs. 1.0 day (0.5–14), p = 0.06.

Conclusion

Among patients with a discharge diagnosis of CHF, there was an association between the use of the PCT assay and both discontinuation of antibiotics given in the ED as well as decreased duration of antimicrobials in patients. These results support the ongoing use of this test to promote antimicrobial stewardship.

Disclosures

All authors: No reported disclosures.
2243. Using Host Biomarkers and Time to Blood Culture Positivity to Predict Necessity for Echocardiogram in Patients with Staphylococcus aureus Endocarditis
Authors: Edwardson Graham , Volk Cecilia , Nizet Victor , Sakoulas George , Rose Warren
Published: October 2019

Background

Patients with complicated S. aureus bacteremia (SaB) require a transesophageal echocardiogram (TEE) to rule out endocarditis. Risks of TEE may exceed benefits in patients with a low pretest probability of endocarditis. Given our prior findings that endovascular bacterial burden drives elevated serum IL-10 concentrations, we hypothesize that time to positive blood culture and IL-10 serum concentrations may be used to risk stratify patients for selection of TEE. We compared time to positive blood culture and serum IL-10 in patients with negative and positive TEE.

Methods

Patients with SaB were included if they had a diagnosis of primary, endovascular infection source of bacteremia identified by an infectious diseases consult team and a TEE performed. A retrospective chart review was done to identify the time to positivity (hours) of patient blood cultures grown aerobically or anaerobically and TEE results. Sera collected at clinical presentation of these patients were tested for biomarkers IL-10 and IL-1β. Mann–Whitney U test compared the data between the two groups.

Results

This study included 66 patients with SaB: 17 with negative TEE and 49 with positive TEE. Patients with a positive TEE confirming endocarditis had a faster time to positive blood cultures compared with patients with negative TEE (P = 0.031; figure). IL-10 serum concentrations were significantly higher in patients with positive TEE (26.2 pg/mL) vs. negative TEE (14.39 pg/mL). Time-to-positivity in blood culture was linearly associated serum IL-10 concentrations (P = 0.044; figure). Serum IL-1β concentrations were also higher in TEE positive vs. TEE negative patients (32.1 vs. 14.7 pg/mL, P = 0.067)

Conclusion

These data lend further evidence to link high endovascular bacterial burden (measured by shorter time to positive blood culture) and serum IL-10 concentrations. As anticipated, patients with positive TEE had significantly shorter time to blood culture positivity and higher IL-10 serum concentrations than those with negative TEE. With further study on a larger number of patients, time to positive blood cultures and serum biomarkers like IL-10 may be used to risk stratify patients for performance of TEE, as well as to select antimicrobial therapy and to adjust treatment duration.

Disclosures

All authors: No reported disclosures.
118. Factors Associated with Positive Follow-up Blood Cultures in Gram-Negative Septicemia
Authors: Hadar Orly , Van Amy , McWilliams Carla , Wulff Luis , Godinez Linda
Published: October 2019

Background

Bloodstream infections remain a significant cause of morbidity and mortality. No guidelines for the management of noncatheter-associated Gram-negative septicemia exist. There is considerable debate regarding the role of 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 were 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 January 1, 2013 through January 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 multidrug-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 that repeating blood cultures in this subset of patients require further study and consideration.

Disclosures

All authors: No reported disclosures.
2256. Baloxavir Marboxil in Combination with Oseltamivir in Two Critically Ill Patients with Influenza A (H1N1; 2009 strain) on Veno-Venous Extra-Corporal Membranous Oxygenation
Authors: Ntem-Mensah Afua Duker , Heil Emily , Pajoumand Mehrnaz , Rabinowitz Ronald , Galvagno Samuel , Schrank Gregory
Published: October 2019

Background

Currently, there are no clinical data regarding the use of baloxavir marboxil in patients with complicated influenza infection. A study in a mouse model of influenza A infection suggested that there may be a potential benefit of combination therapy with neuraminidase inhibitors. We present the first reported use of baloxavir marboxil in combination with oseltamivir in two critically ill patients requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) support due to severe acute respiratory distress syndrome (ARDS) caused by influenza AH1N1 2009.

Methods

Cases: (1) 56-year-old man with a history of coronary artery disease who was vaccinated for flu this season, presented with 5 days of cough and dyspnea and required cannulation for VV-ECMO due to severe ARDS. He was placed on continuous renal replacement therapy (CRRT) for renal failure as well as vasopressor and inotropic support. Bronchoalveolar lavage (BAL) polymerase chain reaction (PCR) was positive for Influenza A H1N1 2009 strain. He received a dose of baloxavir 80 mg on Day 1 and a 7-day course of oseltamivir which was started on Day 0. Influenza PCR testing obtained 5 days after receipt of baloxavir was negative. The patient was decannulated on hospital day 7 and extubated at 14 days. (2) 50-year-old man with a history of hypertension and dyslipidemia who was not flu vaccinated, presented with symptoms of cough and dyspnea for 3 days. He was cannulated due to severe ARDS. He required CRRT for renal failure. BAL PCR tested positive for Influenza A H1N1 2009 strain. He was given two 80 mg doses of baloxavir on hospital days 1 and 5 and treated with oseltamivir for 10 days. Despite a negative PCR test for influenza on day 15, the patient remained critically ill on ECMO with multisystem organ failure.

Results

-

Conclusion

We describe the first reported clinical use of baloxavir in combination with oseltamivir for influenza A H1N1 infection in two critically ill patients with respiratory failure requiring VV ECMO. Further pharmacokinetic/pharmacodynamic analysis is needed to determine optimal dosing in critically ill patients, and those requiring CRRT. Baloxavir synergy with the neuraminidase inhibitors may be of benefit in critically ill patients, and additional prospective clinical study is needed.

Disclosures

All authors: No reported disclosures.
120. The Impact of Early Central Venous Catheter Removal in the Management of Enterococcus Central Line-Associated Bloodstream Infections
Authors: Awadh Hesham , Khalil Melissa , Chaftari Anne-Marie , Fares Johny , Jiang Ying , Deeba Rita , Ali Shahnoor , Hachem Ray Y , Raad Issam I
Published: October 2019

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 with 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 with the non-CLABSI (78% vs. 48%; P = 0.016). Complications were lower in the CLABSI without MBI/CRBSI compared with 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, the 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 with the non-CLABSI group.

Disclosures

All authors: No reported disclosures.
2277. Comparison of 30-day Crude Mortality Rates in Patients with Bloodstream Infections (BSIs) Caused by Colistin Susceptible-(ColS-CRKp) vs. Colistin and Carbapenem-Resistant Klebsiella pneumoniae(ColR-CRKp)
Authors: Tarik Aslan Abdullah , Bıçakçıgil Asiye , Canan Gürsoy Nafia , Liste Ümran , Tozluyurt Abdullah , Otlu Barış , Sancak Banu , Dağ Osman , Sain Güven Gülay , Akova Murat
Published: October 2019

Background

Colistin is a last resort antibiotic against infections with CRKp. Its increased use has led to resistance to this antibiotic.

Methods

This was a single-center, retrospective, cohort study including all CRKp BSIs treated between January 1, 2014 and July 31, 2018. Antibiotic therapy was appropriate if initiated within 5 days from the onset of BSI including at least an active drug with an adequate dosage. Exclusion criteria were missing key data, death < 24 h after inclusion, subsequent episodes in the same patients, pregnancy, polymicrobial BSI, < 18 years of age, no ID consultation, no carbapenemase gene detection by multiplex PCR for blaKPC, blaNDM, blaVIM, blaIMPand blaOXA48. EUCAST breakpoints were used for antibiotic susceptibilities. Colistin MIC was determined by using broth microdilution. FDA criteria were applied for tigecycline susceptibility

Results

Among 174 CRKp BSIs, 129 met all inclusion criteria. Susceptibility to antibiotics was as follows: colistin (51.9%), tigecycline (67.4%), gentamicine (38.0%), amikacin (43.0%), meropenem (32.6%), ciprofloxacin (18.6%), TMP-SMX (24.0%), ceftazidime (7.8%), cefepime (7.8%).

66.1% and 19.4% of the patients received inappropriate therapy in ColR-CRKp and ColS-CRKp groups, respectively (P ≤ 0.001). We incorporated interaction between colistin susceptibility and inappropriate therapy into multivariate logistic regression analysis (MLRA) that was constructed for identification of independent risk factors for 30-day mortality. The variables having P ≤ 0.1 in crude analysis were included in MLRA. After checking correlation between variables by Pearson correlation analysis and multicollinearity analysis, the final model was builded. The results are shown in Table 2.

Conclusion

Colistin resistance and inappropriate therapy were not associated with decreased mortality individually, however their interaction significantly increased 30-day mortality rate (OR: 4.04; 95% CI: 1.62–10.02; P = 0.003).85.5% of ColR-CRKp isolates produced an OXA-48 enzyme which can be inhibited by ceftazidime–avibactam, but not available in our setting, treatment with this agent may have altered the mortality rates. Thus, high rate colistin resistance among CRKp isolates remains as a significant cause of mortality in our setting.

Disclosures

All authors: No reported disclosures.
2281. Ceftolozane–tazobactam (C/T) Treatment Outcomes in Immunocompromised (IC) Patients with Multidrug-Resistant (MDR) Pseudomonas aeruginosa (PA) Infections
Authors: Hart Delaney E , Gallagher Jason C , Puzniak Laura A , Hirsch Elizabeth B , Hirsch Elizabeth B
Published: October 2019

Background

Evaluations of clinical use and real-world outcomes following C/T treatment exist; however, data assessing outcomes in IC patients are limited. This study evaluated treatment patterns and clinical outcomes of IC patients treated with C/T for MDR PA across 15 US hospitals.

Methods

Adult IC inpatients treated for ≥ 24 hours with C/T admitted between 12/14–5/18 for MDR PA infections were included in this retrospective multicenter cohort study. IC was defined as patients with previous solid-organ transplant (SOT), diseases that suppress resistance to infection (HIV/AIDS, leukemia, lymphoma), or receipt of immunosuppressants, chemotherapy, radiation, long-term low-dose (≥ 1 month) or recent high-dose steroids (> 5 days). Clinical and microbiologic data were extracted from electronic records. The primary outcomes were all-cause 30-day mortality and clinical cure, defined as no escalation/additional therapy and improved signs and symptoms from baseline to end of therapy. PA isolates were characterized as MDR if non-susceptible to ≥ 3 classes of antipseudomonal agents. Classification and regression tree (CART) analysis was used to identify the 30-day mortality split in APACHE II scores.

Results

Seventy patients were included; 58 (83%) had received immunosuppressive agents, 47 (67%) had history of SOT, and 19 (27%) had diseases suppressing resistance to infection. Mean patient age was 57 ± 14 years, median (interquartile range) patient APACHE II and Charlson Comorbidity Index scores were 18 (12.5) and 5 (3.75), respectively, with 33 (47%) receiving ICU care at C/T initiation. The most frequent infection sources were respiratory (56%), wound (11%), intraabdominal (10%), and blood and urine (9% each), with 36% having a polymicrobial culture. All-cause 30-day mortality was 19% (n = 13) with clinical cure achieved in 48 (69%) patients. CART analysis identified the 30-day mortality split at APACHE II score > 25 (76% vs. 24%; P = 0.002).

Conclusion

Of 70 IC patients treated with C/T for MDR PA, clinical cure was achieved in 69% and mortality was 19%, consistent with other evaluations reporting on a cross section of patient populations. C/T represents a promising agent for treatment of PA resistant to many traditional antipseudomonal agents in this high-risk population.

Disclosures

Elizabeth B. Hirsch, PharmD, Merck: Grant/Research Support, Research Grant; Nabriva Therapeutics: Advisory Board; Paratek Pharmaceuticals: Advisory Board
2282. Empiric Antimicrobial Therapy and Clinical Outcomes of Infections due to ESBL-producing Klebsiella pneumoniae
Authors: Wendy Fujita Ayako , Clarke Lloyd , Kusztos Amanda E , Doi Yohei
Published: October 2019

Background

Currently, carbapenems are the treatment of choice for invasive infection due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). However, clinical data supporting this practice are generated largely from cases caused by ESBL-producing Escherichia coli. We aimed to describe the empiric treatments and clinical outcomes of patients infected with ESBL-producing Klebsiella pneumoniae (ESBL-Kp) at UPMC Presbyterian Hospital in Pittsburgh, PA.

Methods

This retrospective study included all adult patients from inpatient admissions at UPMC Presbyterian Hospital who were diagnosed with ESBL-Kp infections. Carbapenem-resistant cases were excluded. Types of cultures included blood, respiratory, urine, and wound. Only one type of culture per patient was included. Demographic and clinical data were collected from the electronic medical records. The study was approved by the University of Pittsburgh IRB.

Results

One-hundred sixty-four patients had ESBL-Kp infection between September 2016 and August 2018. Excluded were those who were considered colonized by the organism and therefore not treated (n = 15); treated with non-carbapenems as definitive therapy (n = 29); or were discharged before final susceptibilities (n = 14). In total, 70 patients met inclusion criteria. Eighteen had bacteremia, 24 had pneumonia, 13 had UTI, and 12 had wound infections. Most common sources of bacteremia included catheter-associated, intra-abdominal infection, and pneumonia. Median age of patients was 62 years. Mean Charleston Comorbidity Index was 4.6. Empiric treatment was divided between three classes: BL-BLI (n = 27, 38.6%), cephalosporins (n = 21, 30%) and carbapenems (n = 18, 25.7%). Twelve patients (17.1%) died during hospitalization. Average hospital length-of-stay was 33.2 days.

Conclusion

Although infections with ESBL-Kp are relatively uncommon, patients have high mortality and prolonged hospitalizations. Treatment practices, including which infections are considered colonization vs. true infection, as well as choice of empirical therapy, vary widely at our institution. Data are still needed to assess mortality outcomes in patients treated empirically with carbapenems vs. non-carbapenems, particularly in high-inoculum infection sites such as pneumonia.

Disclosures

All authors: No reported disclosures.
2283. The Incidence and Risk Factors for Neurotoxicity in Patients on Ertapenem Therapy: a Retrospective Case- Control Study
Authors: Fong Raymond K C , Donoghue Stephen G , Shafi Humaira , Yen Tan Seow , Boon Lee Wee , Chiu Kit Wong Edmund , Alalageri Vijaya S , Seah Jonathan
Published: October 2019

Background

Numerous reports have emerged about the neurotoxic effects of ertapenem. A recent study supports carbapenem use for the treatment of extended spectrum β-lactamase (ESBL)- producing Gram-negative bacteremia. This will likely bolster the use of ertapenem as it is a convenient choice to complete antibiotic treatment in an outpatient setting. This study aims to review the incidence of neurotoxicity with ertapenem and the risk factors associated with it.

Methods

A retrospective nested cohort study was conducted in Changi General Hospital in Singapore from January 2015 to Decemeber 2016. All patients who received at least 24 hours of ertapenem were identified. Those who exhibited ertapenem-associated neurotoxic effects were selected as cases while those who did not were included in the pool of controls and randomly selected at a 1:3 ratio.

Results

A total of 544 patients were treated with ertapenem in our hospital during this 2-year period. Twenty-five patients (incidence 4.6%) developed neurotoxic manifestations and 75 patients were included as controls. Acute confusion was the commonest reaction (n = 19, 76%) followed by hallucinations (n = 8, 32%) and seizures (n = 5, 20%). Baseline characteristics were similar in both groups; the median age of the cases was 79 years (IQR 71–83 years) and 14 (56%) were males. The median duration of ertapenem use before neurotoxicity occurred was 7 days (IQR 5–11days). The median Naranjo ADR probability score for cases was 7 (range 5 to 7) which suggests a probable relationship. Univariate analysis showed that renal impairment (with CrCl< 60 mL/minute) (OR 3.31, 95% CI 1.03–10.64), a history of a vulnerable brain (including stroke and epilepsy etc)(OR 2.61 95% CI 1.03–6.61) increased the risk of neurotoxicity. Neurotoxicity was also significantly associated with longer hospitalization (median 21 days, p = 0.03).

Conclusion

Our study suggests that renal impairment or a history of vulnerable brain may increase the risk for ertapenem-associated neurotoxicity. Hence, caution should be exercised when ertapenem is used to treat these individuals. Future prospective studies to further evaluate risk and to derive a prediction scoring system may help to reduce the incidence of neurotoxic adverse events with ertapenem use.

Disclosures

All authors: No reported disclosures.
2284. Treatment and Clinical Outcomes Among Infected Patients with Colistin-resistant Klebsiella pneumoniae Bacteremia.
Authors: Prawang Abhisit , Santimaleeworagun Wichai , Changpradub Dhitiwat , Thunyaharn Sudaluck , Puttilerpong Chankit
Published: October 2019

Background

In recent years, the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) and colistin-resistant Klebsiella pneumoniae (CoRKP) is one of the leading causes of nosocomial infection worldwide. It has become a public health concern and high mortality, which the few treatment options are available. Salvage treatment caused by CoRKP is still unknown. Here, we explored the 14-day and in hospital mortality to understand the threat to clinical and public health. In addition, we determined the treatment regimen for salvage therapy due to CoRKP bacteremia.

Methods

This was a single-center retrospective cohort study conducted from 2016 to 2018. A total of 96 patients with bacteremia were included; they were classified into three groups according to the infected pathogens with non-carbapenem-resistant Klebsiella pneumoniae (non-CRKP); CRKP and CoRKP. Treatment regimen, 14-day mortality and in hospital mortality were reviewed and compared.

Results

Fifty-eight, 10 and 28 patients infected with non-CRKP, CRKP and CoRKP, respectively. The 14-day mortality rate of patients infected with non-CRKP, CRKP and CoRKP was 12.07%, 40% and 60.71%. In hospital mortality was 24.41%, 70% and 82.14%, respectively. All of mortality outcomes had statistically significant different between both of the CoRKP and CRKP group compare to non-CRKP group (P < 0.05). The treatment regimen associated with a favorable outcome on 14-day survival rate in patients with bacteremia due to CoRKP was the antibiotic combination therapy included aminoglycoside (gentamicin or amikacin) with fosfomycin with or without tigecycline. In addition, combination therapy should be avoided prescribing of colistin which supported by lowest survival rate.

Conclusion

Patients infected with CoRKP bacteremia was the highest 14-day and in hospital mortality. However, the new salvage regimen consisting of aminoglycoside with fosfomycin with or without tigecycline combination was associated with favorable the 14-day survival rate.

Disclosures

All authors: No reported disclosures.
2293. Revival of Polymyxins: A Single-Center Historical Cohort of Critically Ill Patients in Brazil
Authors: Maria Dantas de Maio Carrilho Claudia , Bento Talizin Thalita , Lopes Camila R , Patruceli Azevedo Isabella , Paes Kesia , Maria Alves da Silva Leticia , Magalhaes Carvalho Grion Cintia , Tibery Queiroz Cardoso Lucienne , Maria Boll Karine , Alexandrino Servolo Medeiros Eduardo
Published: October 2019

Background

The epidemiological scenario of multidrug-resistant bacteria has brought polymyxins back to medical prescriptions, as they are last-line therapy against carbapenem-resistant bacteria. There is a lack of knowledge of which is the best way to use this drug, especially in critically ill patients. We aimed to evaluate polymyxin use in an intensive care unit (ICU) in a university hospital and to describe its epidemiological characteristics.

Methods

This historical cohort included all consecutive patients who used polymyxins to treat ventilator-associated pneumonia from January 1, 2017 to January 31, 2018, during hospitalization in an ICU from a public university hospital, endemic for carbapenem-resistant bacteria, in Londrina, Brazil. Microbiological processing for diagnosis followed the guidelines from the Clinical and Laboratory Standards Institute (CLSI). Statistical analyses were performed using MedCalc for Windows, version 18.9 (MedCalc Software, Ostend, Belgium) and significance level adopted was 0.05.

Results

There were 179 patients; median of age was 57 years (IQR: 40.0 - 70.75). Polymyxin B was the most prescribed polymyxin (97.2%). Most of the patients had comorbidities (72.6%). Age was higher in the group of patients who died (60.0 vs. 36.5 years, P < 0.0001). Comorbidities prevalence was higher in non-survivors (80.7% vs. 38.2%, P < 0.0001). Sequential Organ Failure Assessment (SOFA) score on polymyxin prescribing day was higher in non-survivors (8.0 vs. 7.0, P = 0.0093), as well as Simplified Acute Physiology Score 3 (SAPS 3) score (70.7 vs. 59.35, P = 0.0003). Thirty-day mortality was 43%. Analysis of 14-day survival showed a higher mortality for patients who had sepsis (Log-rank test, P = 0.0284) and septic shock (Log-rank test, P = 0.0065). Acinetobacter baumannii was the most common etiologic agent, in 125 samples (73.9%), with 97.6% of resistance to carbapenem and 5.6% of resistance to polymyxins.

Conclusion

Polymyxin B was the most prescribed polymyxin. Age was higher in non-survivors, as well as comorbidities prevalence, SOFA and SAPS 3 scores. Patients with sepsis and septic shock showed a 14-day higher mortality. Acinetobacter baumannii was the most isolated agent. Carbapenem resistance was high.

Disclosures

All authors: No reported disclosures.