bluuebunny/crossref_metadata_2025_split huggingface dataset:
2214. Comparison of Cefepime–Zidebactam (WCK 5222), Ceftazidime–Avibactam, and Ceftolozane–Tazobactam Tested Against Gram-Negative Organisms Causing Pneumonia in United States Hospitals in 2018
Authors: Sader Helio S , Carvalhaes Cecilia G , Mendes Rodrigo E , Castanheira Mariana , Flamm Robert K 
Published: October 2019

Abstract

Background
Zidebactam (ZID) is a bicyclo-acyl hydrazide antibiotic with a dual mechanism of action: selective Gram-negative PBP2 binding and β-lactamase inhibition. We evaluated the frequency and antimicrobial susceptibility (S) of Gram-negative bacilli (GNB) isolated from patients with pneumonia in US hospitals.

Methods
All 3,086 clinical isolates were consecutively collected from patients hospitalized with pneumonia (1/patient) in 29 US medical centers in 2018, and the GNB (n = 2,171) were S tested against cefepime (FEP)-ZID (1:1 ratio) and comparators by reference broth microdilution methods. The FEP S breakpoint of ≤8 mg/L (CLSI, high dose) was applied to FEP-ZID for comparison purposes. An FEP-ZID S breakpoint of ≤64 mg/L has been proposed for non-fermentative GNB based on pharmacokinetic/pharmacodynamic target attainment and was applied. Enterobacterales (ENT) isolateswere screened for β-lactamase genes by whole-genome sequencing.

Results
GNB represented 70.3% of the collection, and the most common GNB were P. aeruginosa (PSA; 34.9% of GNB), K. pneumoniae (10.9%), E. coli (9.7%), S. marcescens (7.7%), and S. maltophilia (XM; 6.4%). FEP-ZID was highly active against PSA (MIC50/90, 2/8 mg/L; 98.8% and 99.9% inhibited at ≤8 and ≤16 mg/L, respectively; highest MIC, 32 mg/L), including resistant subsets (table). Among comparators, colistin (99.6%S), ceftazidime–avibactam (CAZ-AVI; 95.2%S), and ceftolozane–tazobactam (C-T; 94.5%S) were the most active compounds against PSA. FEP-ZID inhibited all ENT at ≤4 mg/L, including ESBL-producers (MIC90, 0.25 mg/L) and carbapenem-resistant ENT (MIC90, 4 mg/L). The most active comparators against ENT were CAZ-AVI (99.9%S), amikacin (98.5%S), and meropenem (MEM; 98.3%S). FEP-ZID inhibited 75.0% and 97.9% of XM isolates at ≤8 and ≤16 mg/L, respectively (highest MIC, 64 mg/L). The only other compounds active against XM were co-trimoxazole (MIC50/90, ≤0.12/2 mg/L; 95.7%S) and levofloxacin (MIC50/90, 1/2 mg/L; 70.7%S). FEP-ZID inhibited 71.0% and 98.9% of A. baumannii isolates at ≤8 and ≤64 mg/L,, respectively.

Conclusion
FEP-ZID showed potent in vitro activity against GNB causing pneumonia in US hospitals and may represent a valuable therapeutic option for these difficult-to-treat infections

Disclosures
All authors: No reported disclosures.
2219. Evaluation of Medicare Claims to Assess Burden of Pertussis Disease in Persons Aged ≥65 Years
Authors: Havers Fiona , Wu Xiyuan , Wernecke Michael , Kelman Jeffrey A , Spiller Michael , Hariri Susan 
Published: October 2019

Abstract

Background
Pertussis in adults may be underdiagnosed and underreported; there is limited information on the incidence and severity of pertussis in older adults. We compared pertussis diagnoses identified using medical claims data with national surveillance data to examine the use of claims data as a source for disease burden estimates.

Methods
We examined claims data in persons aged ≥65 years in the United States enrolled in Medicare A and B from January 1, 2008 to December 31, 2017. We identified provider-diagnosed pertussis through pertussis-related ICD9/ICD10 diagnostic codes (033.XX, 484.3, A37.XX). We examined whether any were categorized as inpatient claims and if there were claims for laboratory tests within 30 days of the initial pertussis claim. We estimated claims-based pertussis incidence using person-time for all Medicare A/B enrollees and compared incidence estimates to those reported by the Nationally Notifiable Diseases Surveillance System (NNDSS) for the same period and age group.

Results
Among 27,269,361 Medicare beneficiaries, 24,355 (0.09%) had claims with pertussis diagnostic codes. Of these, 1,875 (7.7%) had claims associated with inpatient hospitalizations; 7,964 (33%) had laboratory testing performed. The mean annual incidence of claims-based pertussis was 11.5/100,000 person-years (range: 9.37 to 14.3/100,000 person-years) (figure). In contrast, 6,722 pertussis cases in persons aged ≥65 years were reported to NNDSS. Among the 5,101 cases whose hospitalization status was known, 783 (15%) were hospitalized. Mean annual reported pertussis incidence was 1.5/100,000 person-years (0.67 cases to 2.63 cases/100,000 person-years) in this age group.

Conclusion
Many more Medicare beneficiaries with pertussis-related claims were identified than pertussis cases in persons ≥65 years reported to public health authorities, suggesting pertussis is likely diagnosed more frequently in older adults than national incidence estimates indicate. A smaller proportion of Medicare beneficiaries with pertussis-related claims were hospitalized compared with reported cases and a majority did not have laboratory testing performed. It is unknown what proportion of pertussis-associated claims represent true pertussis disease.

Disclosures
All authors: No reported disclosures.
2224. Reducing Antibiotic Overuse in Adult Lower Respiratory Tract Infections Using Novel Host–Response-Based Diagnostics
Authors: Shani Liran , Halabi Salim , Shiber Shachaf , Paz Meital , Moscoviz Einat , Neuberger Ami , Petersiel Neta , Grupper Mordechai , Kirshner Dani , Haber Daniel , Kronenfeld Gali , Samuel Mastboim Niv , Gottlieb Tanya , Stein Michal , Rudich Nurit , Sitry Naama , Guetta Claire S , Pri-or Ester , Lishtzinsky Ynon , Yanai Shirly , Maor Yasmin , Oved Kfir , Eden Eran , Drescher Michael , Paul Mical 
Published: October 2019

Abstract

Background
Antibiotic overuse in LRTI is a major healthcare care problem, contributing to antimicrobial resistance. A novel assay that integrates blood levels of three immune-proteins TRAIL\IP-10\CRP was developed to assist in differentiating bacterial from viral disease. The assay exhibited high performance in blinded validation studies focusing on children. We performed a preliminary analysis of the ongoing OBSERVER study, evaluating the assay’s potential to reduce antibiotic misuse in adult patients presenting with suspicion of LRTI.

Methods
OBSERVER (NCT03011515) is an EU Horizon 2020 funded study (grant No. 684589), the first to validate the signature in adult LRTI patients. For every participant recruited at the emergency departments of three hospitals in Israel, we collected medical history, physical examination, routine lab, imaging, and respiratory multiplex PCR data. The assay outcomes are bacterial, viral or equivocal. Reference standard outcome of bacterial, viral, indeterminate or noninfectious, was assigned by expert panel majority adjudication. Indeterminates were excluded from the analysis.

Results
In this preliminary analysis, we included the first 218 patients with locked data (Figure 1). Age ranged from 18 to 96 years (mean 59.5). Clinical syndromes included: 21% pneumonia, 13% acute bronchitis, 6% COPD exacerbation, 32% upper respiratory tract infection and 16% unspecified LRTI or viral infections. The assay demonstrated high diagnostic performance for distinguishing bacterial from viral disease (Figure 2). Assay equivocal rate was 8%. In this cohort, antibiotics were prescribed to 41 of 105 patients with viral reference outcomes indicating an overuse rate of 39%, of these, 34 yielded viral index test outcomes, supporting the potential of the assay to reduce overuse by ~83%.

Conclusion
The TRAIL/IP-10/CRP assay demonstrated high diagnostic performance for differentiating between bacterial and viral disease. Medical literature shows that there is a big gap between guidelines antibiotic prescription recommendations and reported prescribing rates (~25% vs. 40%-50%) for suspected LRTI in adults. The use of this new assay, which has a specificity of 93% and NPV of 99%, can help to close the gap and improve adherence to the guidelines.

Disclosures
All authors: No reported disclosures.
2231. Safety of Nebulized Colistin as Adjunctive Treatment of Lower Respiratory Tract Infections
Authors: Nadeem Komal , Raja Karan , Patel Mitesh , Philips Mona 
Published: October 2019

Abstract

Background
Systemic antibiotics used in treatment of drug-resistant lower-respiratory tract infections (LRTI) may have poor lung penetration or narrow therapeutic indices. Nebulized administration of colistin allows direct instillation of active agent to maximize concentrations at the site of infection. Theoretically, local administration also avoids treatment-limiting toxicities and adverse drug reactions (ADR). Current literature supports efficacy of nebulized colistin as adjunctive treatment for LRTI. However, there is a paucity of data surrounding safety and tolerability of this administration technique.

Methods
The electronic medical record (EMR) was queried to identify patients treated with nebulized colistin between January 1, 2016 and December 31, 2018. The following data were collected from the EMR and hospital ADR reporting systems: demographics, treatment regimen, serum creatinine (SCr), concomitant nephrotoxins, infecting pathogen, treatment-emergent ADRs, and drug toxicities. The primary outcome was prevalence of renal (acute kidney injury [AKI]), neurologic (seizure, visual disturbance), or respiratory (bronchospasm) ADRs secondary to colistin nebulization therapy. AKI was defined according to the RIFLE criteria.

Results
Thirty-two patients were administered nebulized colistin during the study period. Approximately 19% of patients had a baseline renal impairment. Cultures were positive in 29 patients of which 11 organisms were resistant to all tested antimicrobials. The most common infecting pathogen was A. baumanii (n = 15) followed by K. pneumoniae (n = 9). The median duration of therapy was 4.6 days. Seventeen patients (53.1%) were exposed to concomitant nephrotoxins. Three patients experienced AKI of which two received simultaneous furosemide and one had underlying renal dysfunction and received concomitant vancomycin. The one observed neurologic reaction, seizure, occurred in a patient with underlying epilepsy. No patients had documented visual disturbances or bronchospasm.

Conclusion
The results of our study are consistent with the principle that localized administration of colistin results in a lower incidence of systemic adverse events. Nebulized colistin is a safe adjunct for managing LRTI. Renal, pulmonary, and neurologic reactions in this study were likely not treatment-related.

Disclosures
All authors: No reported disclosures.
2245. Oral 5-Day Lefamulin for Outpatient Management of Pneumonia Outcomes Research Team (PORT) Risk Class III/IV Community-Acquired Bacterial Pneumonia (CABP): Post Hoc Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 2 Phase 3 Study
Authors: Schranz Jennifer , Alexander Elizabeth , Fitts David , Mariano David , Meads Andrew , Sandrock Christian , Moran Gregory J , Gelone Steven P 
Published: October 2019

Abstract

Background
Site-of-care decisions (e.g., admission vs. outpatient) in CABP management can be challenging for healthcare providers. Here we describe a post hoc analysis of adults with CABP managed as outpatients in the LEAP 2 double-blind, noninferiority, Phase 3 trial.

Methods
LEAP 2 compared the efficacy and safety of oral lefamulin (LEF) 600 mg every 12 hours for 5 days vs. oral moxifloxacin (MOX) 400 mg every 24 hours for 7 days in adults with PORT Risk Class II-IV. Descriptive statistics were generated to characterize demographics, baseline characteristics, efficacy, and safety outcomes in the subpopulation of outpatients in LEAP 2.

Results
Overall, 42% (310/736) of patients started treatment as outpatients (41% [151/368] LEF and 43% [159/368] MOX). Age, gender, and BMI were generally similar in both treatment groups. 44% (66/151) LEF and 40% (64/159) MOX outpatients had PORT Risk Class III or IV, and 21% in both groups (31/151 LEF and 34/159 MOX) had CURB-65 score 2 or 3. Comorbidities included smoking history (43% LEF vs. 34% MOX), hypertension (26% vs. 30%), COPD/asthma (14% vs. 18%), and diabetes mellitus (7% vs. 11%). Early clinical response (ECR) responder rates and investigator’s assessment of clinical response (IACR) success rates at the test of cure (TOC) visit were high and similar in both groups among all, PORT Risk Class III/IV, and CURB-65 score 2 or 3 outpatients (Table 1). In the PORT Risk Class III/IV subset, 86% LEF vs. 80% MOX patients were both an ECR responder and IACR success at TOC. In the CURB-65 score 2 or 3 subset, 87% LEF vs. 74% MOX patients were both an ECR responder and IACR success at TOC. Treatment-emergent adverse event (TEAE) rates were similar in both groups (Table 2). Consistent with overall study results, the difference between groups in related TEAEs was driven by gastrointestinal disorders (20% LEF vs. 5% MOX), specifically diarrhea (15% vs. 1%). Rates of TEAEs leading to discontinuation were low and similar in both groups. No LEF outpatient had an SAE or was admitted during the study, compared with 5 (3%) SAEs, including 2 deaths, in the MOX group.

Conclusion
These study data suggest that PORT Risk Class III or IV patients can be effectively managed as outpatients with 5 days of oral LEF as an alternative to fluoroquinolones for the treatment of CABP.

Disclosures
All authors: No reported disclosures.
2253. Comparison of Outcomes Between Patients with and without Cystic Fibrosis Treated with Ceftolozane–Tazobactam for Pseudomonas aeruginosa Infections
Authors: Trisler Michael J , Tamma Pranita , Tamma Pranita , Avdic Edina 
Published: October 2019

Abstract

Background
Ceftolozane–tazobactam (C/T) was designed to have enhanced activity against P. aeruginosa and has been shown to retain activity against many isolates that are resistant to other antipseudomonal β-lactams. However, there are no data comparing outcomes in patients with and without cystic fibrosis (CF).

Methods
Retrospective, multicenter cohort study conducted at 5 hospitals that included all patients with P. aeruginosa infections who received C/T as definitive therapy between November 2016 and December 2018. The primary outcome at 90 days was a composite of mortality, recurrence, readmission, and inappropriate response at end of therapy (EOT). The secondary outcome was to describe baseline C/T susceptibility and emergence of resistance. All outcomes were adjudicated by 2 infectious diseases specialists.

Results
Thirty-five, 27 non-CF and 8 CF, patients were included. CF patients were younger, had greater baseline C/T resistance (50.0% vs. 8.3%, P = 0.02) and were more likely to receive combination therapy. The most common site of infection was pulmonary (71.4%) followed by intra-abdominal (14.3%) and osteomyelitis (5.7%). Overall, 54.3% of patients had an unsuccessful outcome with no difference between CF and non-CF patients (62.5% vs. 51.9%, P = 0.70). There was also no difference between each component of the primary outcome. All 4 CF patients with a baseline-resistant isolate had an appropriate response at EOT, while neither of the 2 non-CF patients did. The C/T MIC distribution in CF and non-CF patients was ≤ 2 μg/mL (0.0%, 64.2%), 4 μg/mL (50.0%, 25%) ≥ 8 μg/mL (50.0%, 8.4%). The median duration of C/T in CF and non-CF patients was 18.5 days (interquartile range [IQR], 14–37.5 days) and 15 days (IQR, 10–25 days). Ten, 7 non-CF and 3 CF, patients had a P. aeruginosa isolate cultured and tested for C/T susceptibility within 90 days of index culture with 80% having an MIC increase. Non-CF patients treated for > 14 days were more likely to have an MIC increase (P = 0.047). All CF patients had an MIC increase.

Conclusion
We did not observe a difference in the rate of unsuccessful outcome between CF and non-CF patients; however, our sample size was small. CF patients were more likely to be resistant to C/T at baseline. Resistance emerged frequently in both groups following exposure to C/T.

Disclosures
All authors: No reported disclosures.
2260. Clofazimine Safety and Efficacy for Treatment of Multidrug-Resistant Non-Tuberculous Mycobacteria (NTM)
Authors: Alameer Reem , Pfaeffle Herman , Heysell Scott 
Published: October 2019

Abstract

Background
Nontuberculous mycobacteria (NTM) are increasingly detected and challenging to cure given complex drug-resistance patterns and need to use often intolerable drug multidrug regimens over months to years of duration. As such, NTM infection can be associated with significant mortality and morbidity. Clofazimine is a repurposed drug used in the treatment of leprosy worldwide and increasingly in multidrug-resistant (MDR) tuberculosis. Some centers in the United States have incorporated clofazimine in the treatment of NTM but experience is limited and procurement restrictions have hampered its more widespread use

Methods
A prospective cohort study was performed in patients diagnosed with pulmonary or extrapulmonary NTM infection among those treated with clofazimine from a single center serving referrals from across the state of Virginia under an investigational new drug protocol. Data were collected through the center’s electronic medical record and included both pretreatment and follow-up host characteristics, radiological, microbiological and pathology data. Outcomes were assessed, radiological resolution, symptom improvement, and change in pulmonary function test (among patients with cystic fibrosis).

Results
Thirty-seven patients received clofazimine. NTM species for which the treatment was indicated were M. abscessus in 21 (58%), M. avium complex in 17 (45%) and 3 with M. chelonae. The most common companion drugs for M. abscessus included imipenem, tigecycline, linezolid or tedizolid, amikacin (IV induction followed by inhaled continuation phase) and azithromycin. For other basic patient characteristics refer to Table 1. Survival rate was 97%, while 73.5% had documented improvement in symptoms and only 2.9% had worsening of symptoms. Radiological resolution or partially improving were documented in 38% of the patients. there were no severe adverse events from clofazimine.

Conclusion
Adding clofazimine to multi-class antibiotic regimens for drug-resistant NTM treatment, including pulmonary M. abscessus disease, was well tolerated and led to clinical improvement in the majority of those treated. Randomized controlled studies are needed to determine the individual impact of clofazimine within and otherwise optimized regimen.

Disclosures
All authors: No reported disclosures.
2272. Evaluation of Clinical Features, Carbapenem Resistance and Risk Factors of Klebsiella Species: A 4-Year Retrospective Study in Turkey
Authors: Umit Zuhal , Sahbudak Bal Zumrut , Guner Gizem , Avcu Gulhadiye , Bozkurt Duygu , Kurugol Zafer , Vardar Fadil , Cilli Feriha , Ozkinay Ferda 
Published: October 2019

Abstract

Background
Gram-negative-resistant bacterial infections are increasing due to widespread use of antibiotics. Infections caused by Klebsiella spp. are an important part of healthcare-associated infections and cause morbidity and mortality. The aim of this study was to determine the epidemiological, clinical features, carbapenem resistance rates and risk factors of bloodstream infections of children with Klebsiella spp.

Methods
In this retropective study, medical records of 85 episodes of 75 patients caused by with Klebsiella spp. bacteriaemia who admitted to Ege University Faculty of Medicine, Pediatric Hospital in Turkey between 2014 and 2017 were evaluated. Conventional biochemical methods were performed using the automated systems of MALDİ-TOFF MS / VITEK 2 (Biomerieux, France). According to EUCAST recommendations, VITEK 2 (Biomerieux, France) automated microdilution method was used in sensitivity tests.

Results
The mean age of 85 episodes included in the study was 3.49 (±5.4) years. 58% of the patients were male and 42% were female. 18.8% of the patients were premature. The most common service was newborn service (30.6%). Neutropenia was 26% and thrombocytopenia was 55% at the time of diagnosis. Klebsiella pneumonia was 93% and Klebsiella oxytoca was 7%. Carbapenem resistance rate was found to be 30.6% in Klebsiella spp. Carbapenem resistance was found 18% in 2014, 38% in 2015, 42% in 2016 and 25% in 2017. In patients who developed carbapenem-resistant Klebsiella infection, the duration of pre-hospitalization ≥14 days (P = 0.034), the absolute neutrophil count < 100 (P = 0.048) and steroid use (P = 0.025) were statistically significant risk factors. The mean length of hospital stay was 107 (±103) days. Klebsiella spp. attributable mortality due to infection was 14% and crude mortality was 15%. No statistically significant difference was found in patients who developed resistant and susceptible infections.

Conclusion
Carbapenem resistance in Klebsiella infections was increased. Prolonged hospital stay, neutropenia and steroid use in the last 3 months were identified as significant risk factors for carbapenem-resistant Klebsiella infections.

Disclosures
All authors: No reported disclosures.
2278. Emergence of Resistance and Associated Mortality during Persistent Pseudomonas aeruginosa Bacteremia in Hematopoietic Cell Transplant Recipients and Hematologic Malignancy Patients
Authors: Fontana Lauren , Hakki Morgan 
Published: October 2019

Abstract

Background
Pseudomonas aeruginosa (PSA) bacteremia causes significant mortality in patients with hematologic malignancies (HM) and hematopoietic cell transplant (HCT) recipients in part due to intrinsic and acquired resistance mechanisms. However, the incidence of developing resistance on therapy and the associated outcomes are poorly described. We characterize the emergence of resistance on therapy and describe the outcomes of PSA bacteremia in this population.

Methods
We conducted a retrospective review of adults with HM and HCT recipients who developed PSA bacteremia between January 2012 and April 2018. A bacteremic episode was characterized as ≤ 14 days from the first positive blood culture. Persistent bacteremia was defined as a positive blood culture ≥ 72 hours of appropriate antibiotic therapy. Susceptibility testing was performed with VITEK2. Isolates were classified as “sensitive,” “intermediate,” or “resistant” per standard criteria; “intermediate” and “resistant” results were considered “non-susceptible.”

Results
66 episodes of PSA bacteremia occurred in 59 patients. Among episodes in which a patient survived for ≥3 days, 8 (12.1%) met criteria for persistent bacteremia. Non-susceptibility to therapy developed in 5 of 7 episodes (71.4%) of persistent bacteremia; 1 did not have susceptibilities performed on both isolates. Patients with persistent bacteremia had a second positive blood culture within a median of 3.5 days. A concomitant visceral nidus of infection (pneumonia = 6, soft tissue = 1) (P = 0.005) was identified as the primary risk factor for persistent bacteremia. Risk factors for emergence of non-susceptibility could not be determined due low number of events. Infection associated mortality (IAM) (death ≤ 14 days) occurred in 12 (17.1%) of all episodes and 6 of 8 (75%) of persistent bacteremia. Persistent bacteremia was the only risk factor associated with IAM (P = 0.0002, RR 7.3).

Conclusion
Emergence of resistance to anti-Pseudomonal β-lactam antibiotics frequently occurs during treatment for persistent PSA bacteremia in HCT recipients and HM patients. Persistent bacteremia is associated with a visceral nidus of infection and was the only independent predictor of IAM.

Disclosures
All authors: No reported disclosures.