bluuebunny/crossref_metadata_2025_split huggingface dataset:
2110. Treatment of Coccidioidomycosis with Isavuconazole
Authors: Jamros Christina , Maves Ryan C , Chinn Patricia E , Tang Kathy , Johns Scott T , Fierer Joshua , Berjohn Catherine M 
Published: October 2019

Abstract

Background
There are limited prospective data available to guide the management of severe coccidioidomycosis. In particular, the treatment of disseminated coccidioidomycosis often requires extended courses of antifungal therapy, for which there are often intolerable side-effects, toxicities, and failures. In recent years, newer oral triazole antifungals with in vitro activity against Coccidioides have become available, but data are lacking on their efficacy in coccidioidomycosis. Isavuconazole lacks many of the toxicities of older triazole antifungals, such as QT prolongation and certain key drug interactions, making it an appealing option in selected patients.

Methods
Based on pharmacy prescription history at two federal facilities in southern California, we identified adult patients with coccidioidomycosis who received isavuconazole from 2017 to 2019. Patient records were reviewed to identify age, sex, ethnicity, sites of infection, prior antifungal therapy, indication for switch to isavuconazole, duration of follow-up, and outcomes.

Results
12 patients were identified between the ages of 36 and 86 years; 3 were women. 6 were of Pacific Islander descent, 4 were African American, 1 European-American, and 1 Latino. 6 (50%) had significant pre-infection comorbidities. 8 (67%) had evidence of extrapulmonary dissemination, including 1 patient with meningitis. All but one had received prior treatment with other azoles; two had previously been treated with amphotericin B. Six (50%) were switched to isavuconazole due failure or progression of disease on prior therapy; 3 (25%) due to drug toxicity; and 2 (17%) due to drug interactions. Seven (58%) patients improved on isavuconazole; 4/12 (33%) were stable; one developed hepatotoxicity but improved on posaconazole, and one patient deteriorated.

Conclusion
Isavuconazole appears to be a promising agent for the treatment of coccidioidomycosis. Long-term follow-up will be required to assess the risks of toxicity, disease progression, or relapse. For patients who are clinically stable but with an extensive disease burden or toxicity from older agents, isavuconazole may present an amphotericin-sparing option.

Disclosures
All authors: No reported disclosures.
2117. Fluconazole vs. Echinocandins as Initial Therapy for Candidemia Caused by Fluconazole-Susceptible Species in the Era of Rapid Diagnostic Testing
Authors: Roshdy Danya , Ginn Tyler , Jaffa Rupal K , Anderson William E , Green Elizabeth , Ann Medaris Leigh 
Published: October 2019

Abstract

Background
Echinocandins (ECH) are recommended first-line for initial therapy (IT) of candidemia (CD) over fluconazole (FLU) due to their broad spectrum of activity. This recommendation was made prior to widespread implementation of rapid diagnostic testing (RDT), allowing prompt species identification and targeted therapy. The objective of this study was to compare clinical outcomes in patients with CD caused by FLU-susceptible species who received either FLU or ECH as IT.

Methods
This was a multicenter, retrospective cohort study of adults with CD caused by C. albicans, C. tropicalis, or C. parapsilosis. Patients who received FLU or ECH as IT for at least 48 hours from May 2012 to October 2018 were included. Patients who died within 48 hours of first positive blood culture were excluded. The primary endpoint was the rate of clinical failure (persistent CD for >72 hours, recurrent infection within 30 days, change in therapy, and all-cause mortality within 30 days). Secondary endpoints included 90-day all-cause mortality and time to culture clearance. A subgroup analysis in critically ill patients was conducted.

Results
Of the 371 patients evaluated, 128 met criteria for inclusion, 57 received FLU and 71 received ECH. Patients in the ECH group had a higher incidence of sepsis at the time of first positive blood culture (45.1% vs. 19.3%, P = 0.002). A line-associated source was more common in the ECH group (56.3%) vs. urinary source in the FLU group (21.1%). C. albicans was most common in both groups (63%). Clinical failure was similar in the FLU and ECH groups (38.6% vs. 35.2%, P = 0.69). 90-day mortality and time to culture clearance (1.6 vs. 1.5 days, P = 0.63) did not yield significant differences. In the subgroup analysis of critically ill patients, there was a trend suggesting higher rate of failure in patients who received FLU vs. an ECH (60.9% vs. 47.7%, P = 0.31), though underpowered to detect such a difference. Length of stay (LOS) was shorter in patients who received FLU (12 vs. 18 days, P = 0.018).

Conclusion
FLU as IT for FLU-susceptible CD may be a reasonable option in non-critically ill patients in the setting of RDT. This may lead to shorter LOS given the availability of an oral formulation. Additional prospective studies are needed to validate these conclusions.

Disclosures
All authors: No reported disclosures.
2123. Rapid Phenotypic Detection of Gram-Negative Bacilli-Resistant to Oximinocephalosporins and Carbapenems in Positive Blood Cultures Using a Novel Protocol
Authors: Josa Diego , Bustos-Moya Gisell , Yusef Soad , Crevoisier Stephanie , Silva Edwin , Lopez Natalia , Leal Rafael , Torres Isabel , Pablo Osorio Juan , Arias Gerson , Felipe. Reyes Luis 
Published: October 2019

Abstract

Background
Early and adequate antibiotic treatment are the cornerstones to improve clinical outcomes in patients with Bloodstream infections (BSI). Delays in appropriate antimicrobial therapy have catastrophic consequences for patients with BSI. Microbiological characterization of multi-drug-resistant pathogens (MDRP) allow clinicians to provide appropriate treatments. Current available microbiologic techniques may take-up to 96 hours to identify causative pathogens and its resistant patterns. Therefore, there is an important need to develop rapid diagnostic strategies for MDRP. However, rapid detection techniques are costly and are not widely available. We tested a modified protocol designed to detect Gram-negative bacilli (GNB) resistant to oximinocephalosporins and carbapenems from positive blood cultures.

Methods
This is a prospective, cohort study of consecutive patients with bacteremia. We developed a modified protocol using HB&L® system to detect MDRP. We then attempted to determine accuracy, concordance and reduction of identification time of this novel method in a reference hospital. Descriptive statistics and logistical regressions were used.

Results
Ninety-six patients with BSI were included in the study. A total of 161 positive blood cultures were analyzed. Escherichia coli (50%, 81/161) was the most frequently identified pathogen followed by Klebsiella pneumoniae (15%, 24/161) and Pseudomonas aeruginosa (8%, 13/161). 32% of isolations had usual resistance patters. However, in 29/161 (18%) of identified pathogens were producer of carbapenemasases and 21/161 (13%) of extended-spectrum β-lactamases. Concordance among our HB&L® modified protocol and traditional method was 99% (159/161). Finally, identification times were significantly shorter using our HB&L® modified protocol than traditional methods (Mean, hours [SD], 20.8 [6.22] vs. 62.8 [6.22], P < 0.001).

Conclusion
Here we provided novel evidence that using our HB&L® modified protocol is an effective strategy to reduce the time to MDRP detection/identification; with a great concordance rate when compared with the gold standard. Further studies are needed to confirm these findings and to determine whether this method may improve clinical outcomes.

Disclosures
All authors: No reported disclosures.
2126. Comparison of Time to Appropriate Antibiotic Between Using Microarray Assay and Mass Spectrometry Technique for Identification of Positive Blood Cultures
Authors: Sakulkonkij Parichart , Salee Parichat , Katip Wasan 
Published: October 2019

Abstract

Background
Microarray-based, multiplexed, automated molecular method is a rapid diagnosis of bloodstream infections by directly identify bacterial pathogens and antibiotic resistance by detection resistance genes from positive blood culture. Previous studies showed significantly reduce time to organism identification from positive blood culture and antibiotic resistance gene with 97.1% sensitivity and 100% specificity. This study aimed to evaluate time to appropriate antibiotic between using Microarray Assay and Mass Spectrometry technique for bacterial identification.

Methods
one hundred and forty-five patients with bloodstream infection in medical ward were enrolled between 1 June 2018 and 31 January 2019. There were 2 study periods (pre-intervention and post-intervention), using MALDI-TOF combined with the conventional microbiological method as the current standard diagnostic method in pre-intervention group (N = 70) and microarray technique was used add-on to post-intervention group (N = 75). Antibiotic therapy was adjusted by infectious disease team in both periods of study.

Results
There were significantly faster bacterial identification and detection of antibiotic resistance (39.34 hours vs. 5 hours, P = 0.0001) as well as time to adjust specific antibiotic therapy (75 hours vs. 27.65 hours, P = 0.0001) resulted in earlier appropriate antibiotic therapy (31 hours vs. 0 hours, P = 0.005) and decrease unnecessary of antibiotic adjustment (51.4% vs. 37.3%). However, all-cause mortality within 2 weeks was not significantly reduced (11.4% vs. 14.7%), no differences cost of antibiotic therapy and length of hospital stay (13 days vs. 17 days).

Conclusion
Microarray technique has rapid turnaround time to bacterial identification and detection of some resistant genes. A combination of this technique and clinical judgement encourage earlier appropriateness antibiotic therapy and may be helpful in antibiotic stewardship program.

Disclosures
All authors: No reported disclosures.
2128. Murine Typhus and Pregnancy: Case Series and Literature Review
Authors: Tanabe Melinda , Blanton Lucas , La Rosa de Los Rios Mauricio , Webb Camminati Camille 
Published: October 2019

Abstract

Background
Murine typhus is an arthropod borne disease of worldwide distribution with recent reemergence in the United States of America. There is limited data about the presentation, treatment and outcomes in the pregnant population. We report two cases of murine typhus in pregnancy, as well as a case series based in literature published between 1990 and 2019.

Methods
A comprehensive search in Pubmed database using words murine typhus, pregnancy, R. typhi and endemic typhus was done. Exclusion criteria were asymptomatic murine typhus in pregnancy and undiagnosed febrile illness in pregnancy.

Results
Six articles met the criteria of symptomatic pregnant murine typhus infection. Four case reports plus our own 2 case reports, and 2 observational population studies. A total of 35 pregnancy patients were identified. Distribution was worldwide. Gestational age at presentation varied. Patients frequently presented with prolonged duration of fevers prior to presentation, headache, rash, thrombocytopenia and elevated hepatic transaminases. Diagnosis was mainly based on serology. Treatment varied and 8 cases did not receive any treatment at all. Overall pregnancy outcome was favorable, except in an Asian cohort reporting 6 patients with poor pregnancy outcomes.

Conclusion
The lack of data about murine typhus in pregnancy is of serious concern. Increase awareness of different presentations is needed in this population. Murine typhus infection can mimic other pregnancy-related pathologies that have very different treatments and outcomes. More data are needed about effective treatment and safety of doxycycline use during pregnancy.

Disclosures
All authors: No reported disclosures.
2136. Rapid Antimicrobial Susceptibility Testing using ATP Luminescence and Machine Learning Methods
Authors: Kawabe Shunsuke , Uchiho Yuichi , Noda Hideyuki , Matsui Atsushi , Niimi Hideki , Kitajima Isao 
Published: October 2019

Abstract

Background
To prevent the spread of drug-resistant bacteria, a rapid and accurate antimicrobial susceptibility test (AST) is necessary. Recently, morphokinetic microscopy approaches have been reported as a rapid AST method. However, these still require several hours to obtain a minimum inhibitory concentration (MIC). Adenosine triphosphate (ATP) luminescence has also been reported as a rapid AST method that can detect bacterial growth more rapidly than morphokinetic approaches, since ATP in bacteria increases prior to bacterial division. In this study, we designed a new machine learning-based algorithm that predicts MIC rapidly, using a dataset that contains ATP luminescence patterns and conventional MICs determined by turbidity. Essential agreement (EA) rates between rapid and conventional MIC were then evaluated.

Methods
Sixty-three strains of E. coli (ATCC 25922 and clinical isolates from Toyama University Hospital) were tested. Bacterial suspensions were diluted 500-fold in Mueller–Hinton broth from 0.5 McF solutions, and the final concentration of bacteria was 3×105 CFU/mL. The suspensions were dispensed into a 96-well microplate, which had 12 antimicrobials in two-fold dilution series, and the microplate was incubated at 35°C. At each measurement time point, the amount of ATP in a 10 μL aliquot from each well was evaluated by our original measurement system, which can sensitively detect ATP luminescence equivalent to a single bacterium. After 22 hours, MIC was determined conventionally by measuring turbidity. A rapid MIC for each bacterium was estimated by the algorithm based on the dataset consisting of the rest of the 62 strains (leave-one-out cross validation).

Results
Table 1 shows the EA rate for the 12 antimicrobials; EA rates > 90% were achieved for 7 antimicrobials in 2 hours and for 12 antimicrobials in 3 hours. In 6 hours, an average EA rate > 97% was achieved.

Conclusion
Using the dataset, our new machine learning-based algorithm predicted MIC rapidly within 2 hours with an EA rate > 90% for 7 antimicrobials. The rapid AST detected by the ATP luminescence method will contribute toward both appropriate antimicrobial treatment and reduction in medication and admission charges. In the future, other species of bacteria will be evaluated by our ATP method.

Disclosures
All authors: No reported disclosures.
2143. Attempting to Add Clarity to “Indeterminates” on a Deployed Rapid Diagnostic with Antimicrobial Stewardship Program (ASP) Intervention
Authors: Cox Heather L , Attai April E , Stilwell Allison M , Vegesana Kasi B , Brewster Frankie , Poulter Melinda D , Mathers Amy J 
Published: October 2019

Abstract

Background
Rapid diagnostic testing paired with ASP intervention optimizes therapy and improves outcomes but few data guide ASP response in the absence of organism identification (ID). We describe the microbiology for organisms unidentified by Accelerate Pheno™ Gram-negative platform (AXDX) in order to inform ASP-provider team communication (PTC).

Methods
Consecutive, non-duplicate inpatient blood cultures with Gram-negative bacilli (GNB) following AXDX implementation at a single university hospital between April 2018 and March 2019 were included. Standard of care (SOC) ID and susceptibility followed AXDX. Clinical Microbiology emailed AXDX results to the ASP in real time; results were released into the EMR paired with telephone PTC or withheld after ASP review. Bloodstream Infections (BSIs) and patient outcomes for organisms labeled no/indeterminate ID by the AXDX were characterized.

Results
AXDX was performed on 351 blood cultures. Among 52 (15%) labeled no/indeterminate ID, SOC methods revealed: Enterobacteriaceae (40%; 9 monomicrobial with AXDX targets), anaerobes (21%), non-lactose fermenters (NLFs) other than Pseudomonas aeruginosa (21%), and fastidious GNB (10%). Frequent organisms without AXDX targets included: Raoultella planticola (4); Bacteroides fragilis, Cupriavidus spp., Haemophilus spp., Prevotella spp., Providencia spp., non-aeruginosa Pseudomonas spp., Salmonella spp. (3 each); Pasteurella multocida, Stenotrophomonas maltophilia (2 each). BSI sources were most commonly intra-abdominal (21%), central line-associated (17%), or unknown (17%). CLABSIs were associated with immune suppression and/or substance abuse in all but 1 case. BSIs without active empiric therapy included: NDM-producing Providencia stuartii SSSI; OXA-48-producing R. planticola intraabdominal infection (IAI); Pandoraea spp. CLABSI after liver transplant; enteric fever; B. fragilis, Leptotrichia wadei, and S. maltophilia, each of unknown source. In-hospital mortality occurred in 4 of these cases.

Conclusion
When AXDX yields no/indeterminate ID, ASP chart review for possible anaerobic/IAI, unique environmental exposures, and travel history may assist in guiding empiric therapy. GNB with AXDX targets are not excluded.

Disclosures
All authors: No reported disclosures.
2151. Biofilm and Metallo-β-Lactamase (MBL) Production Among Imipenem-Resistant Pseudomonas aeruginosa and Acinetobacter spp.
Authors: Metok Yang , Hosuru Subramanya Supram , Thapa Shrestha Upendra , Reus Rodrigues Perez Leandro , Adhikari Nabaraj , Nayak Niranjan , Gokhale Shishir 
Published: October 2019

Abstract

Background
Pseudomonas aeruginosa and Acinetobacter spp. head the list of hospital-acquired infections. Resistance to carbapenem as reserve drug is under threat with the emergence of Metallo-β-lactamase (MBL) and biofilm producing bacterial strains. This study was thus undertaken to determine the rate of MBL and biofilm production among imipenem-resistant P. aeruginosa (IRPA) and imipenem-resistant Acinetobacter spp. (IRAS) isolates.

Methods
A total of 79 P. aeruginosa and 117 Acinetobacter spp. were isolated from different clinical specimens of patients visiting Manipal Teaching Hospital, Pokhara Nepal from July 2016 to January 2017. Isolation, identification and antibiotic susceptibility testing of the isolates were performed by standard microbiological techniques. Combined disc test and Epsilometer test (E-test) were employed to detect MBL in IRPA and IRAS isolates. Microtiter plate using crystal violet method was employed for detection of biofilm in imipenem-resistant isolates.

Results
9 (11.4%) of P. aeruginosa and 49 (41.9%) of Acinetobacter spp. were Multidrug Resistant (MDR). Similarly, 22 (27.8%) of P. aeruginosa and 23 (19.7%) of Acinetobacter spp. were Extensively Drug Resistant (XDR). Imipenem resistance was detected among 15 (19%) P. aeruginosa and 57 (48.7%) Acinetobacter spp. isolates. 8 (53.3%) of IRPA and 22 (38.6%) of IRAS isolates were MBL producers while all (100%) of IRPA and 47 (82.5%) of IRAS were biofilm producers. All the biofilm producer IRPA isolates were XDR and 62.5% of XDR IRAS strains were moderate biofilm producers. However, 80% of IRPA, 49.1% of IRAS and 63% of both MBL producer isolates were weak biofilm formers. Polymyxin B and ampicillin-sulbactam showed a better degree of susceptibility against MBL cum biofilm producer IRPA and IRAS isolates respectively.

Conclusion
The study showed high propensity of IRPA and IRAS to form biofilm, which is strongly associated with higher drug resistance. Such high rate of MBL and biofilm producing P. aeruginosa and Acinetobacter spp. alarms the rapid spread of such strains in our hospital setting.

Disclosures
All authors: No reported disclosures.
2156. To Evaluate the Role of Kit-Based Loop-Mediated Isothermal Amplification (TB-LAMP) Assay in the Diagnosis of Tubercular Lymphadenitis
Authors: Nischal Neeraj , Das Saurav , Kumar Singh Binit , Wig Naveet , Soneja Manish , Jorwal Pankaj , Saini Rahul 
Published: October 2019

Abstract

Background
Tuberculosis (TB) is the leading cause of death as a single infectious agent worldwide. In 2017, there were an estimated 1.3 million TB deaths among HIV-negative people and 300,000 deaths among HIV-positive people. The rapid and accurate diagnosis of TB in lymphnode specimens remains a challenging task today. In 2016, World Health Organization endorsed a commercial molecular assay, the LoopAMP™ Mycobacterium tuberculosis complex (MTBC) detection kit (Eiken Chemical Company, Tokyo, Japan), which uses loop-mediated isothermal amplification (LAMP) for sputum samples only. No prospective studies on LAMP in diagnosis of Tubercular Lymphadenitis in adults have been done yet.

Methods
A prospective observational study with a total of 70 lymph-node aspirate specimens from suspected cases of Tubercular Lymphadenitis with age >18 years were selected and subjected to Ziehl–Neelsen staining, LAMP and culture in mycobacterial growth indicator tube (MGIT960). The immunochromatographic test was used to confirm MTB complex (MTBC) in culture positive samples and phenotypic drug susceptibility testing was done using MGIT-960. The composite reference standard (CRS) used in the study includes symptoms, radiological evidence and follow-up of 2 months. 2 × 2 tables were made and Sensitivity, Specificity, PPV, NPV of TB-LAMP were calculated with respect to AFB smear and composite reference standard (CRS).

Results
LAMP assay was able to detect MTBC in 34.3% (24/70) of lymph-node specimens. Sensitivity and specificity of the assay were 100% and 69.7%, respectively, considering smear as gold standard. On comparing with CRS, the assay showed 100% sensitivity and 100% specificity in the diagnosis of MTBC.

Conclusion
In our study, LAMP assay was found to be a promising tool for the diagnosis of Tubercular Lymphadenitis and could be used for rapid and cost-effective diagnosis of Tubercular Lymphadenitis in resource-limited settings.

Disclosures
All authors: No reported disclosures.