bluuebunny/crossref_metadata_2025 huggingface dataset:
1395. Defining the Magnitude of AUC:MIC Driver for Efficacy of the β-Lactamase Inhibitor VNRX-5133 When Combined with Cefepime Against KPC- and VIM/NDM-Producing Enterobacteriaceae and P. aeruginosa
Authors: Daigle Denis , Vernacchio Salvador , Xerri Luigi , Pevear Daniel
Published: November 2018

Background

VNRX-5133 is a cyclic boronate β-lactamase inhibitor (BLI) in clinical development with cefepime for treatment of infections caused by ESBL- and carbapenemase producing Enterobacteriaceae and P. aeruginosa. It is a new generation broad-spectrum BLI with direct inhibitory activity against serine-active site and emerging metallo-β-lactamases (e.g., VIM/NDM). In previous in vivo and in vitro studies, the PK-PD driver of efficacy of VNRX-5133 was defined as AUC:MIC. Described herein are in vitro studies to assess the magnitude of VNRX-5133 exposure (AUC:MIC) required to restore efficacy of cefepime against a broad collection of KPC- and VIM/NDM-producing Enterobacteriaceae (ENT) and P. aeruginosa (PSA) clinical isolates.

Methods

Dose-fractionation studies, consisting of four VNRX-5133 exposures fractionated into regimens administered every 4, 8, 12 and 24 hours, were performed in an in vitro infection model with simulated 2 g q8h dosing of cefepime against NDM-1 producing E. coli. A Hill-type model described the relationship between change in log10 CFU at 24 hours and VNRX-5133 exposure (AUC:MIC), where cefepime MIC was determined with 4 µg/mL VNRX-5133. To evaluate variability of efficacy enabled by VNRX-5133 between isolates as well as between Serine-BL and Metallo-BL producers, dose-ranging studies were completed for eight isolates (seven ENT and one PSA) producing KPC or VIM/NDM metallo-β-lactamases.

Results

The PK-PD exposure parameter AUC:MIC accurately described the efficacy of VNRX-5133 in rescuing cefepime activity against KPC and VIM/NDM carbapenemase-producing isolates of ENT and PSA. The AUC:MIC ratios associated with net bacterial stasis, 1-, and 2-log10 reductions in bacterial burden from baseline were 6.1, 18.4 and 45, respectively, for a collection of five VIM/NDM- and three KPC-producing isolates with cefepime MICs ranging from 4–8 µg/mL with no significant differences observed between Ser-BL and MBL producers.

Conclusion

These data confirm the equivalent in vitro activity of cefepime/VNRX-5133 against organisms producing serine- and metallo-β-lactamases and provides an initial PK-PD target for VNRX-5133 efficacy when used in combination with cefepime for the treatment of ESBL- and carbapenemase-producing ENT and PSA infections.

Disclosures

D. Daigle, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary. S. Vernacchio, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary. L. Xerri, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary. D. Pevear, VenatoRx Pharmaceuticals Inc.: Employee, Salary.
664. Factors Associated with the Need for ICU Care Among Patients with Human Ehrlichiosis
Authors: Kuriakose Kevin , Pettit April , Schmitz Jonathan , Moncayo Abelardo , Bloch Karen
Published: November 2018

Background

Despite the availability of effective therapy, the case fatality rate of human monocytic ehrlichiosis (HME) is 3%, and has been reported to be higher among the immunocompromised. Little is known about predictors of severe disease.

Methods

We performed an observational cohort study at a tertiary care medical center in Nashville, TN. Patients with a positive whole blood or cerebrospinal fluid Ehrlichia polymerase chain reaction between 2007 and 2017 were included. Clinical and demographic data were obtained by chart abstraction. Modified Poisson Regression was used to estimate the adjusted relative risk (aRR) of requiring intensive care unit (ICU) care, adjusting for age, sex, race, Charlson Comorbidity Index, immunosuppression, patient-reported tick exposure, and number of days from first contact with healthcare system to treatment initiation.

Results

We included 155 patients; median age was 48 years, 64% were male, 94% were Caucasian, 74% reported a tick exposure, and 21% were immunocompromised. 28% of patients required ICU care. Immunosuppression and reported tick exposure were associated with a decreased risk of requiring ICU care. An increasing number of days from first contact with the healthcare system to treatment initiation were associated with an increased risk of requiring ICU care.

Conclusion

Twenty-eight percent of patients required ICU care. We found that a delay in initiation of therapy was associated with an increased risk of requiring ICU care. In contrast to other studies, we found immunosuppression to be associated with milder clinical illness, perhaps reflecting a lower threshold to seek care and thus earlier presentation. Patients with recent tick exposure were also less likely to require ICU care, potentially reflecting a higher index of suspicion for HME among providers. Future studies evaluating the impact of provider education on early recognition and treatment may lead to a decreased need for ICU care in patients with HME.

Disclosures

All authors: No reported disclosures.
665. Key Clinical and Laboratory Features in Early Diagnosis of Ehrlichiosis in an Endemic Area of Long Island, New York
Authors: Kaplun Olga , Smith Kalie , Khoo Teresa , Spitzer Eric , Weinbaum Fredric , Marcos Luis A
Published: November 2018

Background

Human monocytic ehrlichiosis (HME) is a tick-borne disease caused by Ehrlichia chafeensis in the northeast United States. Suffolk County, New York has the highest amount of HME cases in NY (176 from 2010 to 2014). Our aim is to identify risk factors for HME and compare clinical presentation and laboratory findings of young vs. older adults.

Methods

A retrospective chart review from January 1, 2014 to December 31, 2017 was performed on all patients ≥18 years who presented to the ER at Stony Brook University Hospital (SBUH) or Stony Brook Southampton Hospital (SBSH) with (i) ICD-9 code 082.4 or ICD-10 code A77.40 and (ii) a positive E. Chafeensis PCR. Data were collected on demographics, clinical presentation, and laboratory results.

Results

Twenty-seven cases of HME were found and separated into Group 1 (G1, n = 10) or Group 2 (G2, n = 17) based on age (Table 1). G1 had a significantly higher chance of being Hispanic than G2. Twenty-four of the 27 patients (89%) were hospitalized with an average length of stay of 3.4 days (range 1–14 days).The only significant difference in clinical presentation was that G1 was more likely to have myalgia (P = 0.02). 40% or more of patients in both groups presented with an acute kidney injury and the average length of hospital stay in days was 4.0 ± 2.9 and 3.2 ± 3.1 for G1 and G2, respectively. The number of cases overall have increased 6.0% per year between 2014 and 2017. Thrombocytopenia presented in all cases.

Conclusion. HME is prevalent in Suffolk County. Clinical presentation and laboratory findings were largely similar between the two groups, except the younger population more often presented with myalgia. A risk factor in this study was to be young and Hispanic, likely due to occupational exposure.

Disclosures

All authors: No reported disclosures.
674. Epidemiology of Diphtheria and Antimicrobial Resistance Among Diphtheria Cases, Bijapur District, Karnataka, India, 2012–2015
Authors: Mohankumar Sree Kalpana , Paschapur Suresh , Mailare Shankareppa
Published: November 2018

Background

India contributes to 80% of diphtheria cases. Many diphtheria outbreaks were reported from Bijapur district of Karnataka state, India. Analysis of burden and drug sensitivity pattern might help to identify risk groups and to provide guidelines for treatment of diphtheria cases. Our objectives were to describe epidemiology and drug susceptibility of diphtheria cases in Bijapur district.

Methods

We did cross-sectional study between 2012 and 2015. We defined a probable case as inflammation of upper respiratory tract with adherent membranes. We defined a confirmed case as a probable case that was laboratory confirmed by throat culture. We collected line list of probable and confirmed diphtheria cases, population details in Bijapur district and antibiotic sensitivity of culture reports. We calculated attack rates and case fatality rate by taluks of Bijapur district. We calculated proportion of antibiotic resistance among lab confirmed cases.

Results

There were 229 probable cases and 26 confirmed cases of diphtheria. Attack rate was 110/million and case fatality rate was 2% (5/255). Median age of males was 5 years (range: 3 months to 18 years) and females was 6 years (range: 1 year to 18 years). Highest attack rate (290/million) was in Bagewadi taluk, followed by Sindagi taluk (130/ million). Attack rate in Bijapur, Indi and Muddebihal were 80, 80and 70 per million respectively. Incidence of diphtheria cases was 3/million in 2012, 15/million in 2013, 80/million in 2014 and 14/million in 2015. Penicillin resistance was found among 92% (24/26) of cases, cotrimaxozole resistance among 27% cases (7/26) and ampicillin resistance among 15% cases (4/26)}. Multidrug resistance for penicillin and cotrimoxazole was found among 23% (6/26) of cases. Multidrug resistance to penicillin and ampicillin was found among 15% (4/26) of cases). All cases were sensitive to azithromycin, erythromycin, doxycycline, clindamycin, ciprofloxacin, cefotaxime, gentamycin and tetracycline.

Conclusion

Diphtheria incidence increased between 2012 and 2014. Incidence reduced in 2015. Penicillin resistance was common. We recommend sensitising health workers about penicillin resistance and educating them not to use penicillin. We recommend estimating vaccine coverage and vaccine effectiveness among children.

Disclosures

All authors: No reported disclosures.
678. Outbreak of Shiga Toxin-Producing Escherichia coli Infections at Marine Corps Recruit Depot (MCRD), San Diego and Camp Pendleton, California: October–November, 2017
Authors: Keaton Amelia , Hassan Rashida , Luna Sarah , Lee Isabell , Magalhaes Richelle , Bidlack Matthew , Graf Paul , Maves Ryan , Smith Linda , Freer Douglas , Flinn Kimberly , Monk Gregory , Trinh Kelly , Crandall John , Noveroske Douglas , Fortenberry Gamola , Peak Corey , McDonald Eric , Waltz Thomas , Patel Kane , Wagner Darlene , Espiritu Jennifer , Christensen Lori , Gieraltowski Laura
Published: November 2018

Background

Shiga toxin-producing Escherichia coli (STEC) infections are a major cause of foodborne illness and the principal cause of hemolytic-uremic syndrome (HUS). In November 2017, CDC and the US Navy responded to an outbreak of STEC illnesses in military recruits at the Marine Corps Recruit Depot in San Diego (MCRD). We investigated to determine the source of this outbreak and identify prevention and mitigation measures.

Methods

In October 2017, medical staff identified a high number of gastrointestinal (GI) illnesses at MCRD. Recruits with diarrhea submitted stool specimens for culture and/or culture-independent diagnostic testing (CIDT) for GI pathogens. We performed pulsed-field gel electrophoresis (PFGE) on culture isolates. Case-patients were defined as confirmed (PFGE-confirmed STEC infection matching outbreak strains), probable (diagnosis of HUS and/or CIDT evidence of STEC), or suspected (bloody diarrhea). We conducted environmental evaluations of dining facilities, training areas, and barracks. A case–control study was performed using PFGE-confirmed case-patients and platoon-matched controls. We performed product traceback for foods identified as exposure risks by interview or case–control study.

Results

We identified 64 confirmed, 105 probable, and 91 suspected case-patients. Thirty case-patients required hospitalization and 15 had HUS. Ages ranged from 17 to 28 years (median: 18 years). Poor hygiene practices among recruits and inconsistent cooking temperatures within dining facilities were noted. Forty-three case-patients and 135 controls were interviewed about food, hygiene, and environmental exposures. Consumption of undercooked beef was significantly associated with illness (mOR 2.40, CI 1.04–5.72, P = 0.04). We identified a single ground beef supplier for MCRD, but dining facility records did not document the dates on which specific lots of ground beef were used.

Conclusion

Case–control analysis and environmental observations suggested undercooked ground beef as a potential source for this outbreak. We recommended the Navy and Marine Corps retain lot information, address food handling concerns, and improve hygiene among recruits.

Disclosures

All authors: No reported disclosures.
689. Narcolepsy During the 2009–2010 H1N1 Pandemic
Authors: Huang Wan-Ting , Yang TienYu Owen
Published: November 2018

Background

In Taiwan, H1N1 vaccination began on November 1, 2009 and coincided with peak H1N1 pandemic activity. Nationwide ecological and case–control studies have identified no substantial association between the use of H1N1 vaccines and narcolepsy; however, wild-type H1N1 virus infection might have triggered narcolepsy onset, or potentially confounded the findings.

Methods

Data collected in the nationwide case–control study was reanalyzed. Confirmed narcolepsy cases (Brighton levels 1–2 for ages 0–15 years and 1–4a for ages at least 16 years) with onset during November 1, 2009–September 30, 2010 were included and ascertained receipt of H1N1 vaccines. We compared incidence of narcolepsy between the H1N1 vaccinated and unvaccinated population and assessed daily cumulative risk throughout the study period, with adjustment for age. We applied population estimates (census data, 2009) and daily doses of H1N1 vaccines administered (Influenza Vaccine Information System) to calculate the number of persons and person-time for each group.

Results

There were 22 narcolepsy cases; five (23%) occurred after H1N1 vaccination. The vaccinated population had higher incidence (1.2 vs. 1.0 per million person-years, P = 0.711) (incidence rate ratio 1.24, 95% confidence interval [CI] 0.40–3.83), and higher cumulative risk (1.1 vs. 0.9 per million persons, P = 0.772) (risk ratio 1.16, 95% CI 0.43–3.14) of narcolepsy (figure). These differences, however, were not significant.

Conclusion

We found comparable average and cumulative risk of narcolepsy between the H1N1 vaccinated and unvaccinated Taiwanese population during the 2009–2010 pandemic.

Disclosures

All authors: No reported disclosures.
693. Congenital Zika Syndrome: Assessing the Fatality Rate Since the 2015 Zika Outbreak
Authors: Neto Nilson N Mendes , Maia Jessika , Queiroz Igor Thiago , Zacarkim Marcelo Rodrigues , Lins Maria Goretti , Labeaud A Desiree , Aronoff David
Published: November 2018

Background

Many studies have demonstrated a causal link between Zika virus (ZIKV) infection, microcephaly (MCP) and other congenital abnormalities (CA). This study aimed to determine the perinatal case fatality rate in cases of Congenital Zika Syndrome (CZS) in the Rio Grande do Norte State (RN), a Brazilian Northeast State highly impacted by the Zika virus outbreak.

Methods

A cross-sectional study was conducted using data obtained through the State Health Department (SHD) for cases of MCP and CA in Rio Grande do Norte from April 2015 to December 31, 2017. Definition of perinatal period: commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth. Perinatal case fatality rate is defined as the number of deaths as a fraction of the number of sick persons with a specific disease (×100).

Results

During the study period, there were 519 cases of MCP and others CA notified in RN, of which 150 were confirmed and 126 remain under investigation. The remaining 243 cases have been ruled out by presenting normal exams or due to presenting microcephaly by non-infectious causes. Of the total confirmed cases, 30.0% (45/150) died after birth or during pregnancy. 64.4% (29/45) of confirmed deaths had ZIKV infection during pregnancy and 4.4% (02/45) had a positive TORCH blood test. The deaths related to Zika were confirmed using either clinical/epidemiological/radiological (the presence of typical and indicative alterations of congenital ZIKV infection) or clinical/epidemiological/serological (RT-PCR and/or IgM/IgG antibodies against ZIKV). Eleven cases remain under investigation and five were ruled out.

Conclusion

This study highlights a high rate of perinatal lethality (64.4%) in cases of CZS. Despite the growing number of CZS cases, the real incidence and prevalence might be higher due to the underreporting and lack of resources for confirmatory diagnostic tests (laboratory and imaging). Due to the high rate of lethality, our findings predict an increase in the infant mortality rate in areas endemic for arboviruses. Because the severe neurological complications caused by CZS, it is likely to pose a substantial burden on public spending on healthcare. This study may be used to better describe the congenital Zika syndrome, its prognosis and natural history.

Disclosures

All authors: No reported disclosures.
696. Mechanism of Cefiderocol high MIC mutants obtained in non-clinical FoR studies
Authors: Ito Akinobu , Nishikawa Toru , Ishii Ryuta , Kuroiwa Miho , Ishioka Yoshino , Kurihara Naoko , Sakikawa Ikue , Ota Takeshi , Rokushima Masatomo , Tsuji Masakatsu , Sato Takafumi , Yamano Yoshinori
Published: November 2018

Background

Cefiderocol (S-649266, CFDC) is a novel siderophore cephalosporin with activity against a wide variety of Gram-negative bacteria including carbapenem-resistant strains. We previously reported that CFDC is efficiently transported into Pseudomonas aeruginosa via iron transporter PiuA. In this study, we examined frequency of resistance of P. aeruginosa to CFDC, and investigated the resistance mechanisms of appeared colonies.

Methods

Frequency of resistance (FoR) was determined by plating an overnight culture of P. aeruginosa PAO1 on Mueller–Hinton Agar containing 4× or 10×MIC of CFDC or ceftazidime (CAZ). Appeared colonies were analyzed by whole-genome sequencing (WGS) to identify genomic mutations. The mRNA expression was determined by real-time RT-PCR, and pyoverdine production was determined by MALDI-TOF/MS and expression of outer membrane protein was analyzed by SDS–PAGE and proteomic analysis.

Results

The FoR to CFDC was 2.9 × 10–8 and <7.1 × 10–8, which were lower than those to CAZ (3.1 × 10–7 and 3.4 × 10–8) in the conditions of 4× and 10×MIC, respectively. MIC of CFDC against CFDC-derived mutant increased from 0.5 μg/mL (MIC against PAO1) to 2 μg/mL, and MICs of CAZ did not increase. In the case of CAZ-derived mutant, MICs of CAZ increased from 1 μg/mL (MIC against PAO1) to 16 μg/mL or higher, though MIC of CFDC did not increase, suggesting no cross-resistance between CFDC and CAZ. WGS identified mutations in upstream regions of pvdS (pvdS mutant), which regulates pyoverdine synthesis, or fecI (fecI mutant), which regulates the synthesis of iron transporter FecA contributing to the transport of iron citrate. The pvdS expression and pyoverdine production in the pvdS mutant were more than 4- and 6-fold higher than those in PAO1, respectively. The expression of fecA in the fecI mutant was more than ninefold higher than that in PAO1.

Conclusion

The MIC increase of CFDC against P. aeruginosa occurred due to the mutation of iron transporter-related genes. The resistance acquisition risks should be low as the frequency of resistance to CFDC was lower and the MIC increase of CFDC against the mutants was smaller than that of CAZ. In addition, no cross-resistance between CFDC and CAZ was observed.

Disclosures

A. Ito, Shionogi & Co., Ltd.: Employee, Salary. T. Nishikawa, Shionogi & Co., Ltd.: Employee, Salary. R. Ishii, Shionogi & Co., Ltd.: Employee, Salary. M. Kuroiwa, Shionogi & Co., Ltd.: Employee, Salary. Y. Ishioka, Shionogi & Co., Ltd.: Employee, Salary. N. Kurihara, Shionogi & Co., Ltd.: Employee, Salary. I. Sakikawa, Shionogi & Co., Ltd.: Employee, Salary. T. Ota, Shionogi & Co., Ltd.: Employee, Salary. M. Rokushima, Shionogi & Co., Ltd.: Employee, Salary. M. Tsuji, SHIONOGI & CO., LTD.: Employee, Salary. T. Sato, SHIONOGI & CO., LTD.: Employee, Salary. Y. Yamano, SHIONOGI & CO., LTD.: Employee, Salary.
699. Relationship Between Klebsiella pneumoniae Antimicrobial Resistance and Biofilm Formation
Authors: Cusumano Jaclyn , Daffinee Kathryn , Luther Megan , Lopes Vrishali , Caffrey Aisling , LaPlante Kerry
Published: November 2018

Background

Klebsiella pneumoniae is a frequently multidrug-resistant organism with a high propensity to form biofilm. K. pneumoniae is the most common carbapenem-resistant Enterobacteriaceae (CRE), and labeled an urgent threat by the CDC. The relationship between K. pneumoniae biofilm formation and specific antimicrobial resistance patterns has not been well defined.

Methods

K. pneumoniae isolates (n = 139) were evaluated for antimicrobial resistance and biofilm formation (CDC, Providence VA Med. Ctr., Rhode Island Hosp., BEI, and ATCC). Susceptibility was based predominantly on 2017 CLSI (Clinical and Laboratory Standards Institute) breakpoints. Isolates were categorized as multidrug-resistant (MDR: resistant to ≥ 1 antimicrobial in ≥ 3 out of 16 antimicrobial categories) or extensively drug-resistant (XDR: resistant to ≥ 1 antimicrobial in all but ≤ 2 out of 16 antimicrobial categories) based on expert consensus criteria for Enterobacteriaceae (European CDC (ECDC)/CDC, 2012). We collapsed antimicrobial categories described by the ECDC/CDC consensus group into nine categories: penicillins, cephalosporins, monobactam, carbapenems, protein synthesis inhibitors, fluoroquinolones, folate pathway inhibitors, fosfomycin, and colistin. Biofilm formation was assessed using a modified crystal violet method (OD570) and defined by tertile cut-points. Antimicrobial resistance was compared for weak (n = 47) vs. strong (n = 46) biofilm formation by chi-square or Fisher’s exact test. Predictors of strong biofilm formation were identified using logistic regression.

Results

MDR isolates were more common among weak (n = 46/47, 97.9%) vs. strong biofilm formers (n = 35/46, 76.1%; P = 0.002), whereas XDR was similar between groups (n = 12/47, 25.5% vs. n = 13/46, 28.3% P = 0.77). Resistance to penicillins, cephalosporins, monobactams, carbapenems, protein synthesis, or fluoroquinolones was more common among weak biofilm formers (P < 0.05). Carbapenem resistance was inversely associated with strong biofilm formation (odds ratio 0.09; 95% confidence interval 0.02–0.33).

Conclusion

Carbapenem-resistant K. pneumoniae was 91% less likely to form strong biofilm. Potential trade-off mechanisms between antimicrobial resistance and biofilm formation require further exploration.

Disclosures

A. Caffrey, Merck: Grant Investigator, Research grant. The Medicine’s Company: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. K. LaPlante, Merck: Grant Investigator, Research grant. Pfizer Pharmaceuticals: Grant Investigator, Research grant. Allergan: Scientific Advisor, Honorarium. Ocean Spray Cranberries, Inc.: Grant Investigator and Scientific Advisor, Honorarium and Research grant. Achaogen, Inc.: Scientific Advisor, Honorarium. Zavante Therapeutics, Inc.: Scientific Advisor, Honorarium.
729. Improved Detection of Adenovirus with the FilmArray Respiratory Panel 2 Panel in a Pediatric Population
Authors: Everhart Kathy , Wang Huanyu , Xu Li , Leber Amy
Published: November 2018

Background

Human adenovirus (ADV) respiratory infections are associated with up to 8% of all identified viral causes of acute respiratory illnesses, especially among young children. They are therefore included as part of multiplex syndromic respiratory testing. Earlier versions of the FilmArray Respiratory Panel were targeted to genogroups B, C, and E. However, all adenovirus genogroups are associated with disease particularly in immunocompromised patients. Recently, a new version of the FilmArray Respiratory Panel 2 (RP2) has been FDA cleared with significant modifications to the adenovirus assay. The goal of this study was to compare the RP2 adenovirus assay to that of the previous version (RP1.7) and our laboratory-developed (LD) adenovirus PCR.

Methods

Analytical comparison: Ten stocks of know adenovirus serotypes representing genogroups A-F were diluted in M4 media and tested on RP2, RP1.7 and LD PCR to determine the relative limits of detection (LOD). Clinical comparison: A total of 423 pediatric nasopharyngeal samples were tested using RP2, RP1.7, adenovirus LD PCR. In addition we performed genotyping PCRs on most adenovirus positive samples based on the availability.

Results

Analytical evaluation revealed that for the 10 serotypes (18, 32, 7, 14, 5, 6, 20, 29, 4 and 40), RP2 showed at least 100-fold increase in sensitivity for six serotypes representing genogroups A, D and F. For B, C and E, the relative LODs were comparable.

In the 423 clinical samples, there was an overall agreement of 94% between RP2 and RP1.7. Among those RP2+/RP1.7− samples (n = 20), 17 samples were confirmed ADV positive by LD PCR. They all had low viral burden (Ct values >30), among them nine samples had sole detections of adenovirus types A, D and F. Five samples were RP2-/RP1.7+, two samples were confirmed by LD PCR and both were type C. Overall, there was a 22% increase in Adenovirus with RP2 compared with RP1.7.

Conclusion

The RP2 adenovirus assay has enhanced inclusivity and lower LOD for all adenovirus genogroups in comparison to RP1.7. Coupled with its faster run time and additional targets, RP2 represents a significant improvement for the syndromic detection of respiratory infections.

Disclosures

A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support.
738. Role of Respiratory Syncytial Virus and Mycoplasma pneumoniae in Pediatric Community-Acquired Lower Respiratory Tract Infections
Authors: Kumar Sanchit , Chakravarti Anita , Kumar Surinder , Kapoor Seema
Published: November 2018

Background

Respiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood and Mycoplasma pneumoniae (M. pneumoniae) is a common cause of respiratory tract infections in all age groups. This study was conducted to determine the role of RSV and M. pneumoniae and in pediatric lower respiratory tract infections employing serological tests, polymerase chain reaction (PCR) and reverse transcriptase PCR analysis.

Methods

In this prospective study, 75 children aged 1 month to 5 years with acute lower respiratory tract infections (LRTIs) were investigated. Paired serum samples were obtained on admission and after 4–6 weeks to assay for M. pneumonia antibodies. Nasopharyngeal aspirates were obtained for the detection of RSV antigen by using the immunochromatographic test, reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and M. pneumoniae by PCR.

Results

RSV infection was positive in 20(60.60%) children aged <1 year and 13 (39.40%) aged 2–5 years, the difference being statistically insignificant (P = 0.360). M. pneumoniae infection was documented in a 15(57.6%) children aged <1 year age and 11(42.4%) in age 2–5 years which was statistically significant(P = 0.026). Clinical and radiological features among RSV and M. pnemoniae positive and negative cases were comparable. Thirty (40%) children were positive for RSV antigen and by RT-PCR and 3(12%) only by RT-PCR. Serological evidence of M pneumoniae infection was documented in 24(32%) children. M. pnemoniae PCR was positive in 8 (10.66%) patients. Together, serology and PCR detected M. pneumoniae in 26(34.66%) children. Considering RT-PCR as a diagnostic standard, the sensitivity of RSV antigen by immunochromatography was 90.90%, specificity 100%, positive predictive value 100% and a negative predictive value of 93.3%.The sensitivity of M. pneumoniae serology was 75%, specificity 73.3%, positive predictive value 25% and a negative predictive value of 96% considering PCR as a diagnostic standard,.

Conclusion

Our data underline the role of RSV and M. pneumoniae as the major cause of community-acquired lower respiratory tract infections in children aged <5 years.

Disclosures

All authors: No reported disclosures.
740. Impact of the 2014 American Academy of Pediatrics Guidance on Respiratory Syncytial Virus Hospitalization Rates for Preterm Infants <29 Weeks Gestational Age at Birth: 2012–2016
Authors: Goldstein Mitchell , Krilov Leonard R , Fergie Jaime , Brannman Lance , Ambrose Christopher S , Wade Sally , Kong Amanda
Published: November 2018

Background

In 2014, the American Academy of Pediatrics stopped recommending RSV immunoprophylaxis (RSV IP) for otherwise healthy infants 29–34 weeks gestational age (wGA), while continuing to recommend RSV IP for infants born at <29 wGA. The decline in RSV IP and associated increase in RSV hospitalizations (RSVH) among infants 29–34 wGA have been described previously, but potential effects of the 2014 guidance change on preterm infants <29 wGA are unknown. This study compared 2012–2014 and 2014–2016 outpatient RSV IP use as well as RSVH rates relative to term infants among otherwise healthy <29 wGA infants.

Methods

Infants born from July 1, 2011 to June 30, 2016 were followed from birth hospitalization discharge through their ﬁrst year of life in the MarketScan Commercial (COM) and Multistate Medicaid (MED) databases. DRG and ICD codes identified term and <29 wGA infants at birth. RSV IP receipt was derived from pharmacy and outpatient medical claims (inpatient RSV IP data were unavailable). RSVH were derived from inpatient medical claims. RSVH IP use and RSVH were assessed across three chronologic age (CA) groups: <3 months, 3–<6 months, and 6–<12 months. RSVH rate ratios for 2012–2014 and 2014–2016 were calculated for <29 wGA infants using healthy term infants 0–<12 months of age as a reference category.

Results

Outpatient RSV IP receipt fell after 2014 for <29 wGA infants across all CA categories, with the greatest decline observed among infants <3 months CA (Table 1). Greater RSVH rates for <29 wGA infants relative to term infants were observed after 2014 (Figures 1 and 2), with infants <3 months CA experiencing the greatest percentage increases in relative RSVH risks.

Conclusion

Outpatient RSV IP decreased and RSVH relative to term infants increased among otherwise healthy <29 wGA infants following the 2014 policy change, even though RSV IP continued to be recommended. The effects were greatest for infants <3 months CA and those insured by Medicaid.

Funded by AstraZeneca

Disclosures

M. Goldstein, AstraZeneca/MedImmune: Consultant, Research grant and Research support. L. R. Krilov, AstraZeneca/MedImmune: Consultant, Research grant and Research support. J. Fergie, AstraZeneca/MedImmune: Consultant and Speaker’s Bureau, Research grant and Research support. L. Brannman, AstraZeneca: Employee, Salary and Stocks. C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks. S. Wade, Wade Outcomes Research and Consulting contracted by Truven: Consultant, Consulting fee. A. Kong, Truven Health Analytics, an IBM Company: Employee, Salary.
748. The Impact of a Positive Respiratory Viral Panel Among Hospitalized Adult Patients with Negative Rapid Influenza Testing at an Academic Tertiary Care Facility: A-matched Cohort Study
Authors: Ciccone Emily , Kinlaw Alan , Chundi Vahini , Miller Melissa , Weber David , Juliano Jonathan , Jhaveri Ravi , Willis Zachary ,   The UNC Antimicrobial Stewardship Team
Published: November 2018

Background

Multiplex nucleic acid amplification assays (NAATs) are increasingly used to evaluate respiratory illnesses. Viral diagnosis has the potential to change clinical management and, specifically, decrease antibiotic use. However, the assays are expensive, and their effect on clinical management is unknown. This study evaluated the incremental impact of a multiplex respiratory viral panel after negative rapid influenza testing.

Methods

We completed a retrospective review of all adult patients with respiratory viral panel (RVP; GenMark) and/or rapid influenza or RSV/influenza PCR tests (PCR; Cepheid Xpert) collected within 48 hours of admission to non-ICU, inpatient units from September 1, 2015 to April 15, 2016. We matched hospitalizations with a positive RVP simultaneously with or following negative PCR testing (PCR−RVP+) 1:1 with patient encounters with negative rapid PCR testing only (PCR−). Matching of the referent PCR-group occurred without replacement based on age (±10 years), sex, race, season of testing (±50 days), and any respiratory viral test in the prior 30 days. The primary outcome was a change in management, defined as antimicrobial de-escalation (discontinuation, switch from intravenous to oral administration, and/or narrowing of spectrum), antiviral initiation, and/or change in isolation precautions.

Results

During the study period, there were 153 PCR−RVP+ patient encounters and 524 with PCR− testing only from which we identified 134 matched pairs. In the matched cohort, the median age was 60 years (IQR: 41–71), 47.8% were female, and 34.3% were non-White. Respiratory viral testing was associated with management change in 3.7% of PCR− and 23.9% of PCR−RVP+ patients (risk difference 20.1%; 95% CI 12.2–28.0%). Antimicrobial de-escalation did not occur after testing for any PCR- patients but did occur for 15.7% of PCR−RVP+ patients (95% CI 9.5–21.8%).

Conclusion

Among patients with negative rapid influenza testing, a subsequent or simultaneous positive RVP was associated with a higher frequency of antibiotic de-escalation. This suggests multiplex NAATs could play a role in improving antimicrobial stewardship in the setting of respiratory illness.

Disclosures

M. Miller, GenMark: Investigator, Research support. R. Jhaveri, GenMark: Investigator, Research support.
752. Geographic Analysis of Latent Tuberculosis Screening: A Health System Approach
Authors: Bonnewell John , Farrow Laura , Dicks Kristen , Cox Gary , Stout Jason E
Published: November 2018

Background

Targeted testing and treatment of latent tuberculosis infection is a key element of tuberculosis (TB) elimination in the United States. In particular, foreign-born persons from TB-endemic countries are high priority for latent TB screening.

Methods

We used the DEDUCE interface to query the electronic medical records of all patients presenting to Duke University Health System from January 1, 2010 to November 1, 2017. Latent tuberculosis screening was identified using CPT codes for the tuberculin skin test (TST) and/or interferon gamma release assays (IGRA). Patients’ home addresses were mapped to census tracts; demographic data for these tracts were obtained from the American Community Survey. Higher-risk foreign born persons were defined as persons born in Africa, Asia, or Latin America.

Results

Thirty-six thousand eight hundred and twenty-five patients received 48,419 TSTs and 5,366 received 5,746 IGRAs during the study period. Excluding census tracts with fewer than 20 Health System patients (to reduce referral bias), census tracts with a higher proportion of higher risk residents had a greater proportion of Health System patients screened for latent TB (P < 0.001, figure). Health system patients residing in census tracts with greater proportions of higher risk foreign born residents were more likely to be screened with TST than with an IGRA (P < 0.001).

Conclusion

Latent TB screening was significantly but weakly associated with a greater proportion of higher risk foreign born persons in a given census tract, and persons residing in such tracts were more likely to be screened with TST, which is not preferred due to cross-reaction with the BCG vaccine. Focusing latent TB screening on higher risk areas and using more IGRAs will be necessary to optimize TB prevention efforts.

Disclosures

All authors: No reported disclosures.
755. Clinical Adherence to Latent Tuberculosis Screening Recommendations in Adults with Inflammatory Bowel Disease (IBD) Prior to Biologic Therapy
Authors: Mponponsuo Kwadwo , Fisher Dina
Published: November 2018

Background

Biological agents have become increasingly common in the treatment of immune-mediated illnesses. Their use, however, is associated with an increased risk of progression from latent to active tuberculosis (TB) infection. The American Thoracic Society (ATS) recommends both a tuberculin skin test (TST) and an interferon gamma release assay (IGRA) be conducted to screen for latent TB prior to initiation of biologic therapy. We examined the adherence to these recommendations for adults with inflammatory bowel disease (IBD) in the Calgary region of Alberta.

Methods

In this retrospective cross-sectional study, we used the Alberta Health Services’ Sunrise Clinical Manager and Netcare databases to identify IBD patients initiated on biologic therapy (age >18 years) in Calgary, Alberta between 2008 and 2018. Socio-demographic and clinical characteristics of patients were described. Linear and logistic regression models were constructed to identify factors associated with screening. All analyses were conducted using Stata 15.0 (University of London, UK).

Results

There was a total of 247 identified cases (48.18% female). Of these 96 were Ulcerative Colitis and 151 Crohn’s Disease. The mean age was 39.5 (14.8 SD). There was a total of 210 (85%) who had documented screening with the TST and nine (3.4%) with the IGRA. In a multivariable analysis, factors associated with latent TB screening were age and outpatient setting at the time of screen. Six patients (2.43%) had positive screens and four of those six were treated for latent TB infection.

Conclusion

TST remains the predominant screening method for latent TB infection although the ATS recommends both IGRA and TST prior to biologic therapy. Screening varied with age and higher rates were noted in those evaluated as outpatients compared with inpatients. Further work is needed to evaluate the barriers to screening and to improve access to latent TB screening particularly in the inpatient setting.

Disclosures

All authors: No reported disclosures.
767. A 7-Year Retrospective Study of Pediatric Tuberculosis in a Third-Level Hospital in Mexico City
Authors: Saldaña Napoleón González , Parra Mercedes Macías , De La Garza Eduardo Arias , Trujillo Diego Galvis , Ayala Salim Kuri , Macías Ernesto Rivera , Bejarano José Iván Castillo
Published: November 2018

Background

According to WHO data, in 2016 10.4 million people were infected with tuberculosis (TB), from which one million were patients ≤18 years, and 250,000 deaths. The diagnosis of TB in pediatric patients is a challenge given the clinical behavior.

Methods

This is a retrospective, descriptive, and observational study of patients under 18 years treated at the TB Clinic at Department of Pediatric Infectious Diseases in the National Institute of Pediatrics (INP) in Mexico City during the period 2011–2018.

Results

A total of 118 cases were included; 64 (54.5%) were male, and the average age at diagnosis was 79.45 ± 63.7 months. The most frequent presentations were; lymph node in 50 (42.4%) cases, followed by skeletal 20 (16.9%), pulmonary 16 (13.6%), meningeal 11 (9.3%), abdominal 6 (5.1%), cutaneous 6 (5.1%), and miliary 4 (3.1%). The most common symptoms were fever (52%) and lymphadenopathy (49%). TST was applied in 42 cases (55% positive). A positive COMBE was reported in 47.5% of patients. We performed: GeneXpertâ in 33 (28%) cases with 36% positive results; biopsy in 74 (62%) cases with 92% positive cases; and Ziehl-Neelsen stain in 30 (25.4%) cases with 26% positive results. Positive cultures (41%) isolated: M. bovis 25 (52.4%), followed by MTB complex in 9 (19%), M. tuberculosis 7 (14.3%) and atypical Mycobacteria with 7 (14.3%) cases. The most frequent treatment was: INH (98.2%), RIF (95.5%), E (85.6%) and PZA (77.5%) with an average of 6.3 months during intensive phase and 10.1 months of maintenance. Primary immunodeficiency (PID) was detected in 33 (20.3%) cases, mainly: chronic granulomatous disease in 15 (45.5%), Mendelian susceptibility to Mycobacterial diseases was found in 8 (24.2%) and severe combined immunodeficiency in 7 (21.2%). Overall mortality was 2.5%.

Conclusion

Tuberculosis in Mexico is still a major public health problem and thus is important to remain suspicious of it. This is the first report in Mexico where immunodeficiency is investigated in pediatric patients with tuberculosis, detected in one out of five cases, which stresses the need of its search, given this can modify the outcome.

Disclosures

All authors: No reported disclosures.
779. Mycobacterium tuberculosis Prosthetic Joint Infections: A Case Series and Literature Review
Authors: Uhel Fabrice , Corvaisier Grégory , Poinsignon Yves , Chirouze Catherine , Béraud Guillaume , Grossi Olivier , Varache Nicolas , Arvieux Cédric , Berre Rozenn Le , Tattevin Pierre ,   Groupe d’Epidémiologie et Recherche en Infectiologie Clinique Centre-Ouest (GERICCO)
Published: November 2018

Background

Mycobacterium tuberculosis is a rare cause of prosthetic joint infection (PJI), as most countries with high prevalence of tuberculosis have limited access to arthroplasty. We aimed to characterize the diagnosis, the management, and the outcome of M. tuberculosis PJI.

Methods

All cases of M. tuberculosis PJI documented in a network of 7 referral centers in France were retrospectively reviewed. Data were collected from medical files on a standardized questionnaire, including diagnosis, management, and outcome. In addition, we performed a systematic literature review using the keywords”prosthetic joint,” and”tuberculosis.”

Results

During years 1997–2016, we managed 13 patients (8 males, 5 females, median age 79 years [range, 60–86]) with documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to PJI diagnosis was 9 years [0.4–20]. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months [6–32]). Nine patients underwent surgery: debridement (n = 4), definitive resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. One patient died of disseminated tuberculosis. The literature review identified 70 additional cases of documented M. tuberculosis PJI, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement and prosthesis retention, 86% (19/22) with revision arthroplasty, and 81% (17/21) with definitive prosthesis resection (NS).

Conclusion

M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment.This case series and literature review suggest that the paradigms for the management of M. tuberculosis PJI may differ from PJI related to other pathogens, for which surgery is required.

Disclosures

All authors: No reported disclosures.
781. Non-Tuberculous Mycobacterium: Often a Missed Entity
Authors: B Sairam , Gogia Atul , Kakar Atul , Byotra S P
Published: November 2018

Background

Initially referred to as Lady Windermere syndrome, the prevalence of Non-Tuberculous Mycobacterium (NTM) is on the rise globally. In India, the TB capital of the world, these infections still go unrecognized, as the clinical presentation of all mycobacterial diseases are similar. This is of clinical relevance as misdiagnosis may lead to unwarranted or inappropriate therapy.

Methods

We conducted a retrospective study of adults suspected of having mycobacterial infection. Records of patients admitted with suspected TB from January 2015 to December 2017 were reviewed; clinicoradiological features were correlated with the organism isolated; treatment given and outcomes were recorded.

Results

Out of 877 suspected patients, 245 patients had microbiologically proven Mycobacterium tuberculosis and 34 had NTM (3.8%). Pulmonary infection was seen in 19 cases (56%), rest were extra pulmonary (34%).

Fever was the commonest symptom (62%) others being cough (50%), breathlessness (41%), hemoptysis (15%), weight loss (3%), chest pain (3%), and back ache (12%). Symptoms were prolonged (>1 month) in 65% of cases. Radiologically, cavitations (42%), lung nodules (32%), and infiltrates (32%) were commonly seen. Upper zone predilection was noted in 68% of cases. Past tuberculosis was the major risk factor seen in 42% of cases while 26% were immunocompromised. Macrolide resistance was noted in none of our patients. Twenty-four out of 34 cases were AFB smear positive (71%), but MTB gene Xpert was negative. Our series includes four patients who did not respond to first-line anti-tubercular therapy (ATT) and were suspected to have multi-drug-resistant (MDR) tuberculosis. Cultures later grew NTM and the patients improved with macrolide regime.

Conclusion

NTM is an underreported infection in a developing country like India with a high TB prevalence. Similar clinical features and morphology create a greater diagnostic dilemma. Usage of molecular techniques and AFB culture should be made mandatory in all suspected cases of tuberculosis. NTM should always be considered in ATT nonresponders before starting them on MDR regime.

Disclosures

All authors: No reported disclosures.
784. The Changing Epidemiology of Disseminated Mycobacterium avium complex in the United States
Authors: Dousa Khalid M , Ponce-Terashima Rafael , Van Aartsen Daniel , De La Hoz Alejandro , Johnson John L
Published: November 2018

Background

The epidemiology of disseminated Mycobacterium avium complex (DMAC) infection in the United States is changing. Previously most DMAC occurred in adults with advanced AIDS. Since the development of effective antiretroviral therapy, the incidence of DMAC in AIDS has fallen more than 10-fold. Malignancy, immunosuppression, and tumor necrosis factor inhibitors are known risk factors for DMAC. We sought to describe the epidemiology of DMAC disease in HIV seronegative patients in the United States.

Methods

We performed a retrospective analysis of a commercial database (Explorys Inc., Cleveland, OH). This database contains an aggregate of Electronic Health Record data from 26 major integrated healthcare systems in the United States from 1999 to present. Explorys contains de-identified information from over 50 million patients, 360 hospitals, and over 317,000 providers. We identified a total of 571 persons diagnosed with DMAC, based on Systemized Nomenclature of Medicine-Clinical Terms. We excluded 80 HIV-infected and identified association of the infection with known risk factors.

Results

Of 570 patients, 491 HIV-uninfected patients with DMAC were studied. Underlying structural pulmonary diseases were COPD and bronchiectasis (51% and 47%, respectively). Two hundred ten patients had concomitant malignancy of which lung cancer was the most frequent (43%). Seventy-nine percent were receiving corticosteroids and 10 patients (2%) were on TNF inhibitors (2%).

Conclusion

In this study, majority of patients with DMAC are HIV-uninfected. Larger studies should focus on identifying the prevalence and risk factors of DMAC in the post-AIDS era.

Disclosures

All authors: No reported disclosures.