bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.