bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world Evaluation of Ceftolozane/Tazobactam (C/T) Use and Clinical Outcomes at an Academic Medical Center in Las Vegas
Authors: Leuthner Kimberly D , Kullar Ravina , Jayakumar Becky , Hewlett David A , Nguyen Truong , Puzniak Laura 
Published: October 2017

Abstract

Background
There is a global increase in Gram-negative (GN) pathogens, with Enterobacteriaceae and Pseudomonas aeruginosa(PSA) being the major threats in clinical practice. C/T is a novel antipseudomonal cephalosporin combined with an established β-lactamase inhibitor, approved for the treatment of complicated intra-abdominal and urinary tract infections. The objective was to describe the real-world clinical use and outcomes associated with C/T.

Methods
This retrospective descriptive study included adult patients treated with C/T &gt; 48 hours from July 1, 2015–February 28, 2017 at University Medical Center of Southern Nevada. Treatment was considered empiric when antibiotic was given prior to culture results. Escalation was the additional of an aminoglycoside or colistin after the start of C/T.

Results
There were 30 patients in the study. Average age was 57 (SD = 16) and most 19 (63%) were male, Caucasian 22 (73%) and were admitted from the community or home 18 (60%). The most frequent comorbidities were diabetes 13 (43%), heart disease 12 (40%) and chronic pulmonary disease 10 (33%). Previous medical history within 90 days included 15 (50%) hospitalizations, 13 (43%) infections, 6 (20%) Intensive Care Unit stays and 7 (23%) surgeries. All patients received a GN antimicrobial within 30 days prior to C/T. Ninety-three percent of infections were due to PSA and 17 (57%) were polymicrobial. All but 4 patients had multidrug-resistant PSA. The most frequent source of infection (some multiple sources) was respiratory 20 (67%), cUTI 8(27%) and sepsis 5 (17%). Empiric C/T therapy was given to 7 (23%) patients. One patient required escalation of therapy after C/T. Average duration of C/T was 10 (SD = 5.4) days. 23 (77%) patients were discharged within 30 days of last dose of therapy. Microbiological eradication was documented for 12 patients. There were 5 (17%) readmissions, but none associated with a GN infection. Six patients died (1 bilateral stroke, 1 cancer, 2 septic shock, 1 pneumonia and 1 complications of burn).

Conclusion
In this study, C/T was used in patients with serious infections primarily due to PSA, with most patients discharged within 30 days and no patients readmitted due to GN infection. This study provides important insights on how C/T is used in clinical practice.

Disclosures
R. Kullar, Merck & Co., Inc.: Employee, Salary. B. Jayakumar, Merck: Grant Investigator, Research grant. L. Puzniak, Merck: Employee, Salary.
Breaking New Ground: An Evaluation of Susceptibility Breakpoints for Echinocandins against Candida Species
Authors: Bader Justin C , Andes David R , Castanheira Mariana , Ambrose Paul G , Bhavnani Sujata 
Published: October 2017

Abstract

Background
The increasing prevalence of resistant Candida species has led to renewed interest in evaluating the utility of echinocandins. PK-PD target attainment analyses are increasingly used to inform decisions about susceptibility breakpoints. We carried out such analyses to evaluate anidulafungin, micafungin, and caspofungin Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints for C. Albicans, C. glabrata, and C. parapsilosis.

Methods
Monte Carlo simulations (n = 2000) were conducted using published population PK models [J Clin Pharmacol 2004; 44:590–598, ICAAC 2008; Abstr A-011, AAC 2013; 57:1664–1671]. The following labeled intravenous dosing regimens for the treatment of candidemia were evaluated: anidulafungin 200 mg followed by 100 mg daily, micafungin 100 mg daily, and caspofungin 70 mg followed by 50 mg daily. Day 1 free-drug plasma AUC values were calculated for simulated patients after administration of each agent. Free-drug plasma AUC:MIC ratio targets associated with 1-log10 CFU reductions from baseline of C. Albicans and C. glabrata for anidulafungin, micafungin, and caspofungin, derived from neutropenic murine disseminated candidiasis models, were used [AAC 2007; 52:539–550, AAC 2010; 54:2497–2506]. Similar such targets for C. parapsilosis were utilized to evaluate caspofungin and micafungin. Percent probabilities of PK-PD target attainment were computed by MIC. The results were evaluated in the context of MIC distributions for each pathogen from a collection of isolates obtained worldwide from 2014 to 2015 [ECCMID 2017; Abstr P1748].

Results
Among the CLSI susceptibility breakpoints evaluated, only one was supported by the analysis results shown in Figure 1 (caspofungin vs. C. glabrata), and only one other susceptibility breakpoint was within one dilution of the highest MIC at which the percent probability of PK-PD target attainment was ≥90% (anidulafungin vs. C. glabrata). All other susceptibility breakpoints were ≥2 dilutions above this MIC.

Conclusion
These results demonstrate the need to re-evaluate the echinocandin susceptibility breakpoints for Candida spp. Establishing appropriate susceptibility breakpoints will ensure appropriate prescribing and optimal patient outcomes.

Disclosures
All authors: No reported disclosures.
Impact of an Extended Infusion Β-lactam Strategy on Outcomes in Critically Ill Patients with Pseudomonas Infections
Authors: Klinker Kenneth , Venugopalan Veena , Carnley Andrea , Voils Stacy , Cope Jessica , Cherabuddi Kartikeya 
Published: October 2017

Abstract

Background
Pseudomonas aeruginosa (PSA) is frequently associated with nosocomial infections resulting in significant morbidity and mortality. High MICs in MDR strains highlights the need to maximize antibiotic exposure with the goal of improving patient outcomes. For β-lactams, optimal efficacy is achieved when free drug concentrations are above the MIC for ~ 40–60% of the dosing interval. Unfortunately, due to significant pharmacokinetic variability in the critically ill, achieving this target with standard intermittent infusions (II) is challenging, resulting in preference for extended (EI) or continuous infusion strategies. Additional data in patients with PSA infections are needed to understand the association between infusion strategy and clinical outcome.

Methods
A single-center, retrospective chart review. Adult patients with positive respiratory or blood cultures for PSA treated with cefepime or piperacillin/tazobactam managed in an ICU from January 2012 to May 2016 were included. Primary endpoint was clinical cure (CC) at end of therapy (EOT) between patients receiving EI or II. Secondary endpoints included microbiologic eradication (ME), 28-day mortality, length of ICU and hospital stay, and effect of baseline kidney function on clinical cure.

Results
Eighty-three patients were included in the analysis. Patient characteristics were well matched except for a higher frequency of malignancy in the EI arm (P = 0.02). CC was achieved in an overwhelming majority of EI patients compared with II (89.2% vs. 69.6%, P = 0.031). Further, patients with normal renal function (CrCL ≥ 60; P = 0.02) or APACHE II ≥ 17 (P = 0.04) receiving II experienced higher failure rates. In multivariate analysis, use of II associated with 4-fold higher incidence of clinical failure (OR 4.5 [1.3–16.3]). For other secondary endpoints, ME was observed in 73% of EI vs. 65% of II (P = 0.44) and 28-day mortality was observed in 13% of patients in both arms (P = 0.94). No significant differences were observed with other secondary variables.

Conclusion
Use of an EI strategy in critically ill patients with PSA infections improves CC. Further, EI benefitted those patients with normal to augmented renal clearance suggesting that improved exposure may play a role in clinical outcomes.

Disclosures
K. Klinker, The Medicines Company: Scientific Advisor, Consulting fee.
Assessing the Risk of Nephrotoxicity Associated With Non-renally Adjusted Intravenous Polymyxin B Compared with Traditional Dosing
Authors: Maniara Bejoy , Doan Thien-Ly , Healy Lauren 
Published: October 2017

Abstract

Background
Prior data states that polymyxin B is renally cleared and thus required renal adjustments, however newer data suggests that polymyxin B undergoes non-renal clearance. With more aggressive dosing, potential for increased nephrotoxicity is of concern. This study aims to determine whether time to acute kidney injury (AKI) differs between renally adjusted and non-adjusted doses of intravenous (IV) polymyxin B. Secondary objectives aim to evaluate incidence of AKI, length of stay (LOS), adverse reactions, and potential role of ascorbic acid in decreasing nephrotoxicity.

Methods
This retrospective chart review compared time to AKI in patients receiving renally adjusted and non-adjusted IV polymyxin B between Jan 2012 and Nov 2016. This study included patients who are at least 18 years old, received IV polymyxin B, and have creatinine clearance below 80 mL/minute. Patients were excluded if they had AKI (RIFLE criteria), received renal replacement therapy, or are pregnant prior to receipt of IV polymyxin B. Fine and Gray’s model for competing risks was used to predict the cumulative incidence function of AKI. Descriptive statistics, two-sample t-test, and Chi-square test were used as appropriate.

Results
Of the 132 patients screened, 54 met inclusion criteria (23 in the renally adjusted vs. 31 in the non-adjusted group). There was no statistical association between dosing type and time to AKI (P = 0.13). Incidence of nephrotoxicity was higher in the renally adjusted vs. non-adjusted groups (21.7% vs. 6.5% respectively). Mortality was higher in the renally adjusted vs. non-adjusted groups (17.4% vs. 6.5% respectively). LOS was greater in the renally adjusted vs. non-adjusted groups (16 vs. 14 days respectively, P = 0.26). All patients in the study received concomitant nephrotoxic agents (e.g., vancomycin, aminoglycosides). Ascorbic acid use was infrequent but, in the 4 patients who did receive it, none developed AKI. No difference in neurotoxicity, respiratory arrest, Clostridium difficile infections was seen.

Conclusion
No significant association between IV polymyxin B dosing type and time to AKI was found. Incidence of AKI, LOS, and mortality was higher in the renally adjusted group compared with the non-adjusted group. Ascorbic acid may mitigate the nephrotoxic potential of IV polymyxin B, but further studies are needed.

Disclosures
All authors: No reported disclosures.
Zika Virus Epidemic in the Dominican Republic, 2016
Authors: Peña Farah , Pimentel Raquel , Khosla Shaveta , Mehta Supriya , Brito Maximo 
Published: October 2017

Abstract

Background
The first cases of Zika (ZIKV) in the Americas were reported in Easter Island, Chile in 2014. The epidemic spread to Brazil and Central America in 2015. We describe the extent and distribution of the countrywide ZIKV epidemic in the Dominican Republic.

Methods
The DR Ministry of Health (MoH) instituted active surveillance, monitoring and mandatory reporting of suspected cases of ZIKV in 2015 through the National System of Epidemiologic Surveillance (SINAVE). In the pre-epidemic period, the MoH conducted active search and blood testing of suspected cases in communities rumored to have cases of the disease. During the epidemic, the MoH conducted weekly monitoring of all cases of febrile exanthems, flaccid paralysis and meningitis, and also conducted rapid surveys in highly populated areas to identify local outbreaks. Data from SINAVE was exported and analyzed using SAS.

Results
A total of 5226 cases ZIKV were reported to the MoH from January 2016 to December 2016 (figure). Cases were 74% female, of whom 1275 (33%) were pregnant. Most of the cases (51%) were diagnosed in the age group of 20 to 39, and did not differ by gender. The majority (58%) of cases were reported from a metropolitan area. Almost all cases (82%) were treated in the outpatient setting, while 17% were hospitalized. Only 3 patients died and 95% had an uncomplicated course. There were 285 cases of Guillain BarrŽ Syndrome (GBS; Figure), with the epidemic curve showing a peak 2–4 weeks following the peak of the epidemic. Compared with patients with suspected ZIKV (n = 1054), those with GBS were more likely to be male (47% vs. 19%, P &lt; 0.001), aged ≥40 years (53% vs. 19%, P &lt; 0.001),, more likely to have complications (18% vs. 6%, P &lt; 0.001) and comorbidity (2% vs. 0.2%, P = 0.04) Seventeen (6%) of confirmed GBS cases resulted in death.

Conclusion
The DR reported one of the largest ZIKV outbreaks in the Americas. The epidemic started early in 2016 and had all but subsided by May 2017. Although most cases had an uncomplicated course, incidence of GBS was high.

Disclosures
All authors: No reported disclosures.
Zika Virus Serologic Diagnosis by NS1 ELISA in Curacao
Authors: Manuel Samantha , Virginia-Cova Liane , Joseph Loubiela , Roggeveen Chris , Steingrover Radjin 
Published: October 2017

Abstract

Background
Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV.

Methods
ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity.

Results
Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay.

Conclusion
In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern.

Disclosures
All authors: No reported disclosures.
Utilizing an Equitable and Multifaceted Zika Screening Tool to Identify At-Risk Individuals For Testing and Education: Successes, Challenges, and Lessons Learned in Harris County, Texas.
Authors: Haynie Aisha , Martinez Diana , Jin Sherry , Piper Tamisha , Reed Brian , Shah Umair A 
Published: October 2017

Abstract

Background
Harris County Public Health (HCPH) is the health department for Harris County, Texas jurisdiction, representing 2.3 million residents. Located in the nation’s Third most populous county, HCPH’s 13 wellness clinics and WIC centers provide services for over 100,000 patients annually.
Since late 2015, HCPH confirmed 46 individuals with Zika infection/disease, including two infants with microcephaly and congenital disease. Over two-thirds of these infections were in individuals of Hispanic origin, including all twelve infected pregnant women, two of whom were unaccompanied minors.
Due to Harris County’s geographic vulnerability to Zika, highly mobile residents, and HCPH’s largely low-income Hispanic and refugee clinic population, equitably screening and educating patients about Zika exposure is of paramount importance.

Methods
Using U.S. CDC guidelines, HCPH developed a multifaceted Zika Screening Tool (ZST) for use within clinics. Front desk staff, outreach workers, nursing staff, and clinical providers all participate in various portions of the education-based screening process. The ZST is updated as new CDC guidance becomes available.

Results
All pregnant and high-risk patients received Zika education. Forty-five patients, mostly pregnant females, were additionally referred for testing and further care.

Conclusion
HCPH’s ZST successfully identified high-risk patients for education and testing. This presentation will explore HCPH’s equity-based rationale for education-oriented screening, the ZST’s evolution over time, and describe ZST forms and their integration into the clinic visit. Successful implementation strategies, challenges, and lessons learned will also be discussed, along with the role of the ZST as an integral part of HCPH’s overall multidisciplinary Zika response effort.

Disclosures
All authors: No reported disclosures.
Are New Biomarkers Useful in the Diagnosis of Meningitis in Adults?
Authors: Aksoy Firdevs , Yilmaz Gürdal , Aydin Nurten Nur , Kaya Selcuk , Karahan Süleyman Caner , Koksal Iftihar 
Published: October 2017

Abstract

Background
Meningitis is infection of the central nervous system with high mortality and morbidity in adults. Markers for diagnostic purposes can therefore be useful guides in differential diagnosis. Procalcitonin (PCT), platelet distribution width (PDW) and red blood cell distribution width (RDW) can be easily calculated with automated blood systems, and have been regarded as biomarkers showing inflammation in infection-related diseases. The purpose of this study was to determine the diagnostic significance of these biomarkers in adult meningitis.

Methods
This study was a retrospective investigation. Diagnosis of meningitis was based on clinical findings and microbiological and biochemical investigations of CSF specimens. Patients’ white blood cell count (WBC), C-reactive protein (CRP), PDW, RDW and PCT levels at time of presentation were compared. P &lt; 0.05 was regarded as statistically significant.

Results
137 patients were assessed. Ninety-five patients had acute bacterial meningitis (ABM), 17 had aseptic meningitis (AM) and 25 had chronic meningitis (CM). When patients were evaluated by age, AMB was more common in the elderly and AM in the young (P &lt; 0.05). CRP and PCT levels at presentation were significantly higher in AM than in AM and CM (P &lt; 0.05). WBC levels differed statistically significantly between ABM and CM (P &lt; 0.05). PDW levels were significantly higher in AM then in CM (P &lt; 0.05). RDW was statistically significantly higher in CM than in ABM and AM (P &lt; 0.05). When ROC analysis was performed to differentiate ABM from the other forms (table). Correlation analysis between CSF biochemistry and biomarkers revealed that PCT was positively correlated with CRP, PDW and CSF protein and negatively correlated with CSF glucose.

Conclusion
Our results suggest that PCT and CRP have diagnostic characteristics in favor of ABM at differential diagnosis in cases in which LP is contraindicated and/or CSF examination cannot be performed immediately or the agent cannot be identified. WBC and RDW can be useful guides in differentiating ABM from CM, and PDW and RDW in differentiating CM from ABM and AM.

Disclosures
All authors: No reported disclosures.
Achieving Optimal Specialty Cerebrospinal Fluid (CSF) Testing: Are Electronic Medical Record Order Sets Helpful?
Authors: Abrantes-Figueiredo Jessica I , Bieluch Virginia M , Nailor Michael D 
Published: October 2017

Abstract

Background
Specialty PCR testing has become available for lumbar puncture to determine the cause of infectious meningitis and encephalitis. Testing with low pre-test probability may increase antimicrobial therapy while results are pending and create increased direct costs. We aim to describe the appropriateness of testing before and after the implementation of electronic medical record (EMR) order sets designed to reduce excessive testing of CSF by creating two lists of tests: (1) a routine panel for all patients and (2) a list of optional specialty tests designed to be utilized after the nucleated cells are resulted.

Methods
Retrospective study of adult patients undergoing lumbar puncture with suspicion for CNS infection pre-and post-implementation of EMR order sets from January 2016–March 2017. Consecutive patients with complete charts were reviewed from a tertiary care center. Data collected included demographics, co-morbid conditions, clinical presentation, and lumbar puncture results. The primary outcome of interest was the frequency of CSF specialty testing in patients with ≤ 10 nucleated cells/µL in the CSF.

Results
Two hundred patients had ≤ 10 nucleated cells/µL in the CSF (n = 108 in pre-EMR group; n = 92 in post-EMR group). Of these patients 74% and 48.9% had Herpes Simplex Virus (HSV) PCR testing done pre and post EMR changes (P &lt; 0.05). Enterovirus PCR testing remained similar among both groups (37% pre-EMR order sets vs. 36.9% post-EMR order sets, P = 0.99). Lyme PCR testing decreased between pre- and post-groups (26.8% vs. 9.7%, P &lt; 0.05). CSF Epstein-Barr virus PCR testing also dropped significantly from 26.9% to 7.6% (P &lt; 0.05). All specialty PCR testing that was performed on patients with ≤ 10 nucleated cells/µL in the CSF were negative. Paradoxically, HSV antibody testing increased post-implementation of EMR order sets (21.7% vs. 0%, P &lt;0.05). Total costs of tests on average decreased by $70.71 per patient post EMR changes.

Conclusion
In this cohort, CSF specialty testing was common but decreased after EMR changes. Laboratory stewardship can be improved with EMR changes but further education is needed to prevent unnecessary tests. Unwanted tests (HSV antibodies) may be increased as prescribers are unable to locate familiar tests.

Disclosures
M. D. Nailor, Astellas: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium. Merck: Grant Investigator, Research grant.