bluuebunny/crossref_metadata_2025_split huggingface dataset:
773. Statins Decrease the Risk of Active Tuberculosis: A Propensity Score-Matched Analysis
Authors: Kim Min-Chul , Yun Sung-Cheol , Kim Sung-Han 
Published: November 2018

Abstract

Background
Statins, which are lipid-lowering agents, have anti-inflammatory and immunomodulatory properties that may affect the development of tuberculosis (TB). We assessed the association between statins and the risk of active TB with propensity score-matching.

Methods
The study was based on the National Health Insurance database and its subset database of the “medical check-up” population of South Korea. These cohorts consist of about one million and 570,000 people, respectively, representative of the entire population of South Korea. We identified 107,689 statin users and 433,067 nonstatin users. After propensity score matching, 26,036 statin users and the same number of nonstatin users were finally analyzed. The development of active TB was monitored in these matched pairs over the 11 years from 2003 to 2013.

Results
The number of active TB cases was 150 in 31,645 person-years (4.74 per 1,000 person-years; 95% CI, 3.98 to 5.50) in the statin users, and 902 in 153,401 person-years (5.88 per 1,000 person-years; 95% CI, 5.50 to 6.26) in the nonstatin users. Statin users had a significantly lower risk of TB than nonstatin users: hazard ratio (HR) 0.78 (95% CI, 0.65 to 0.93) (P = 0.006). A subgroup analysis showed that statin use reduced the risk of TB significantly in subjects without diabetes but not in subjects with diabetes: HRs were, respectively, 0.73 (95% CI, 0.56 to 0.95) (P = 0.018) and 0.83 (95% CI, 0.54 to 1.28) (P = 0.40).

Conclusion
These epidemiologic findings provide strong evidence that statin use decreases the risk of active TB. The protective effect of statins against TB was attenuated by diabetes. Further studies about the effect of statins on TB incorporating experimental and clinical researches are required.

Disclosures
S. H. Kim, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI): Investigator, Grant recipient.
786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
Authors: Dousa Khalid M , Kreiswirth Barry N , Kurz Sebastian , Bonomo Robert A 
Published: November 2018

Abstract

Background
Mycobacterium abscessus harbors a β-lactamase enzyme, BlaMab, able to hydrolyze penicillins, most cephalosporins and carbapenems. As of today, management of M. abscessus with β-lactams does not include combination of β-lactamase inhibitors. The potential benefit of combinations of several β-lactams with new diazabicyclooctane (DBO) inhibitors, such as relebactam and avibactam, has not been well studied. Based upon the ability to inhibit BlaMab by highly potent DBO inhibitors, our goal herein was to investigate the efficacy of a novel combination, ceftaroline (CEF) and avibactam (AVI), to restore susceptibility to β-lactam antibiotics and inhibit growth.

Methods
Minimum inhibitory concentrations (MICs) of CEF with or without AVI were examined using the microdilution method.

Results
MIC50 and MIC90 of CEF is 8 mg/L; in the presence of 4 μg/mL of AVI, the MICs of CEF decreased to ≤4 mg/L in 31 of 35 cases (table).

Conclusion
Our results add to the growing evidence of using β-lactams as agents effective against Mycobacterial infections. Inhibition of the hydrolytic activity of (BlaMab) using DBOs such as AVI suggest that this combination should be evaluated in animal and clinical models.

Disclosures
All authors: No reported disclosures.
787. The Addition of Avibactam Augments the Activity of Piperacillin Against Mycobacterium abscessus in vitro, and Is Effective in Treating M. abscessus Infection in a Galleria mellonella in vivo Model
Authors: Meir Michal , Barkan Daniel 
Published: November 2018

Abstract

Background
Mycobacterium abscessus is an emerging multi-drug-resistant pathogen, harboring the β-lactamse BlaMAB. Avibactam is a non-β-lactam, β-lactamase inhibitor shown to inhibit BlaMAB and improve the efficacy of ampicillin for M. abscessus infections in in vitro and in vivo models. Whether the addition of avibactam to piperacillin enables use of the latter against M. abscessus is unknown

Methods
We used a recombinant, luminescent M. abscessus to measure the reduction of MIC to meropenem, ampicillin, and piperacillin induced by avibactam. We then used our previously established G. mellonella infection model (Figure 1)1 to evaluate the effect of antimicrobial treatments in vivo.

Results
Addition of avibactam (4 µg/mL) consistently decreased MIC of ampicillin and piperacillin by 16 and 16–32-fold, respectively, but as expected had no significant effect on meropenem MIC (Figure 2). We inoculated 60 G. mellonella larvae with luminescent M. abscessus on day 0, and treated larvae with meropenem, piperacillin, avibactam alone, or piperacillin combined with avibactam on days 2 and 3. Using IVIS® imaging, we measured infection progression in live infected larvae on day 4. Larvae treated with meropenem and piperacillin–avibactam had significantly lower infection burden compared with untreated controls (P &lt; 0.0001 and P = 0.004, respectively). Piperacillin and avibactam alone had no significant inhibitory effect (Figure 3).

Conclusion
Our findings suggest that the piperacillin–avibactam combination is effective against M. abscessus infections. This novel combination may hold a great promise for patients with cystic fibrosis suffering from M. abscessus, Pseudomonas aeruginosa, and/or Staphylococcus aureus co-infections. The G. mellonella infection model may be used in future studies to assess the efficacy of various antimicrobials and antimicrobial combinations on M. abscessus, P. aeruginosa, and S. aureus co-infections.
Reference
1. Meir M et al. Antimicrob Agents Chemother. 2018.

Disclosures
All authors: No reported disclosures.
790. The Efficacy of the Interferon-γ Releasing Assay-Based Isoniazid Treatment for Preventing Active Tuberculosis in Kidney Transplant Recipients: A Quasi-experimental Study
Authors: Kim Hae-In , Jo Kyeong Min , Choi Sungim , Jung Kyung Hwa , Park Jung Wan , Yun Ji Hyun , Kim Min Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Shin Sung , Kim Young-Hoon , Han Duck Jong , Kim Sung-Han 
Published: November 2018

Abstract

Background
Interferon-γ releasing assays (IGRAs) are useful for diagnosing LTBI. However, there are limited data on the efficacy of IGRA-based isoniazid (INH) treatment with/without back-up tuberculin skin test (TST) to prevent the development of TB in solid-organ transplant recipients.

Methods
All adults patients admitted to a KT unit from January 2014 to December 2016 were retrospectively reviewed in a 2,700-bed, tertiary-care hospital in Seoul, South Korea. The IGRA (i.e., QuantiFERON-In-Tube) with/without TST was performed on all recipients before KT, and 9-month INH treatment was given to patients with clinical risk factors for LTBI regardless of IGRA results. Our hospital policy on LTBI diagnosis and treatment was changed as follows. Period 1 (January 2014–September 2015) adopted IGRA-based INH treatment. We administered INH treatment to all patients with positive IGRA results. Period 2 and period 3 adopted IGRA-based followed by back-up TST-based INH treatment. Period 2 (October 2015–December 2015) included the temporary shortage of Mantoux test, so INH treatment was not given to the patients with positive IGRA since back-up TST was not performed. In Period 3 (January 2016–December 2016), we administered INH treatment to the patients with positive IGRA results followed by back-up TST¡Ã10 mm. The development of TB after KT as the primary endpoint was observed from January 2014 to April 2018.

Results
The study flow is shown in Figure 1. Of the 1,150 KT recipients, 14 (1.2%) developed TB (incidence rate 0.63 per 100 person-years, 95% CI 0.35–1.06). The median time for TB development was 9.4 months (IQR 4.7–14.5). Seven (3.2%) of 216 patients with positive IGRA without INH treatment developed TB, whereas none of 106 patients with positive IGRA with INH treatment developed TB (rate difference 2.43 per 100 person-years, P = 0.008) and 7 (0.8%) of 828 patients with negative or indeterminate IGRA results developed TB (rate difference 2.0 per 100 person-years, P &lt; 0.001). The number needed to treat (NNT) for IGRA-based INH treatment was 31 (95% CI 18–114).

Conclusion
IGRA-based INH treatment is effective to prevent the development of TB in KT recipients without clinical risk factors for LTBI with reasonable NNT.

Disclosures
All authors: No reported disclosures.
798. The Role of Whole-Genome Sequencing in Characterizing the Mechanism of Action of Anti-Tuberculosis Compounds: Demonstrated With Para-Amino Salicylic Acid and Its Analogue
Authors: Satta Giovanni , Witney Adam A , Ere Diepreye , Disney Alex , Begum Neelu , Canseco Julio Ortiz , Ratledge Colin , Boa Andrew N , McHugh Timothy D 
Published: November 2018

Abstract

Background
Para-aminosalicylic acid (PAS) was one of the first antibiotics to be used against tuberculosis (TB) and it is still one of the last remaining drugs available to treat extensively drug-resistant (XDR) disease. Despite being on the market for decades, the mechanism of action of PAS is not completely understood yet. Sixteen new compounds against Mycobacterium tuberculosis were created in the laboratory as salicylate analogues (based on their chemical structures) and their antimycobacterial activity had never been tested before. The main aim of this project was to test the activity of these new analogues and to understand their mechanism of action (including PAS).

Methods
The compounds were tested using three different methods (spot culture, resazurin, and MGIT system). Additionally, resistant mutants were created against PAS and the most promising analogue; whole-genome sequencing (WGS) was performed to understand their mechanism of action.

Results
One compound in particular, AD25a, showed the lowest critical concentration (0.04 µg/mL) among the salicylate analogues. The WGS analysis identified a total of 28 single nucleotide polymorphisms (SNPs) in the AD25a-resistant mutants and 40 SNPs in the PAS-resistant mutants (when compared with the reference strain H37Rv). The SNPs identified in the AD25a and PAS-resistant mutants did not overlap. The genes rrs, rrl and folC were mostly involved in the PAS-resistant mutants.

Conclusion
The complete difference in the mutation profiles suggests that AD25a has a mechanism of action different to that of PAS, despite AD25a being synthesized as a salicylate analogue. WGS analysis of PAS-resistant mutants has also provided some interesting results. In particular, all our PAS mutants showed mutations in the rrs and rrl genes (16S and 23S RNA genes, respectively). These mutations should affect the ribosomes and the overall synthesis of proteins. This highlights a new potential mechanism of resistance for PAS that has never been observed before.

Disclosures
All authors: No reported disclosures.
800. Drug-Resistant TB: An Experience From Qatar
Authors: Ali Maisa , Alhowady Faraj , Munir Waqar , Almaslamani Muna , Alkhal Abdulatif , Alswaidi Zubiada , Ziglam Hisham 
Published: November 2018

Abstract

Background
Drug-resistant tuberculosis (DR-TB) is an important issue for public health. This study was conducted to evaluate the characteristics, treatment outcome, and risk factors associated with 223 DR-TB cases in the State of Qatar.

Methods
A descriptive records-based retrospective study was conducted on patients registered at Communicable Disease Centre (CDC), Qatar to all consecutive microbiologically confirmed tuberculosis cases for the period January 2010–March 2015. Demographic and clinical data extracted included: patient’s age, sex, and country of origin; disease site (pulmonary or extra-pulmonary); presence of comorbidities, HIV/AIDS status, previous chemoprophylaxis and/or previous treatment for TB, and anti-TB drug resistance the resistance pattern of isolated mycobacteria. The sputum culture conversion rate and treatment outcome was assessed for the patient who completed their treatment in Qatar

Results
Of 3,301 patients with positive M. tuberculosis culture were analyzed; 223 (6.7%) were resistant to one or more first-line drugs, to isoniazid in 3.1% (n = 102), streptomycin in 1.2% (n = 41), rifampicin in 0.2% (n = 6), ethambutol in 0.15% (n = 5), and multi-drug resistance in 1.2% (n = 38) of patients. Among the resistant TB patients, more common demographic characteristics were former resident of Indian subcontinent (64.1%). A history of anti-TB treatment was not a risk factor with drug resistance in our cohort. Only 111 (49.7%) patients were tested for HIV antibodies and the results were all negative. There was significant correlation between the type of drug-resistance and CXR finding (23.3% had cavity—P = 0.019). Sputum culture conversion to negative at 2 month of therapy was 94% (n = 101), whereas 122 cases lost follow-up. The outcome of treatment was assessed for 85 resistant cases with follow-up after completion of treatment, show cure rate of 97.6%, and relapse of 2.4%. However, 137 cases (61.4% from total) they left the country before completion of therapy.

Conclusion
Drug-resistant TB in Qatar is influenced by migration, especially from the Indian subcontinent, where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation, and drug susceptibility testing should be the standard of care to avoid further transmission and improve TB control.

Disclosures
All authors: No reported disclosures.
984. Maternal and Infant Factors Influencing Influenza Vaccination Among Young Children Born in Colorado From 2008 to 2016
Authors: Alishahi Musheng , De Crescenzo Lauren , Rao Suchitra 
Published: November 2018

Abstract

Background
Factors influencing influenza vaccination in the first 2 years of life are important to identify and target strategies to increase vaccination rates, since this group is at high risk of morbidity from influenza. The objectives of our study were to determine maternal and neonatal factors associated with influenza vaccination in the first 2 years of life.

Methods
We conducted a retrospective cohort study using linked data from the Colorado Birth Registry Database and the Colorado Immunization Information System of live births between 2008 and 2016. Our population was limited to singleton, first births with first varicella vaccination documented in the immunization registry. Our primary outcome was receipt of at least one influenza vaccination in children ≤2 years. Exploratory variables included maternal (number of prenatal visits, urban vs. rural residence) and infant factors (term birth, admission to neonatal intensive care [NICU] at birth). Multivariable logistic regression was used to assess the association between these factors and influenza vaccination.

Results
Among 126,763 births in the cohort, 50.2% were vaccinated against influenza by 2 years of age. Mothers of unvaccinated children were older (27 vs. 26 years), married (67.8% vs. 66.8%), and more likely to have at least some college education (25.4% vs. 24.1%). A higher proportion of infants admitted to the NICU or who received oxygen were unvaccinated compared with vaccinated (8.5% vs. 8.0% and 2.5 vs. 2.1, respectively), P &lt; 0.001 for all. There were no differences between urban vs. rural residence. In adjusted/stratified analyses, an increase in pre-natal visits was associated with a decrease in early influenza vaccination (IR = 0.992, 95% CI 0.986– 0.998, P = 0.0084 for Hispanic mothers and IR = 0.984, 95% CI 0.973–0.996, P = 0.0069 for non-Hispanic mothers). After adjusting for maternal age, preterm birth, and oxygen at birth, children admitted to the NICU were less likely to be vaccinated (IR = 0.915, 95% CI 0.873–0.959) against influenza by 2 years.

Conclusion
There were statistically significant differences in maternal and neonatal factors between unvaccinated and vaccinated children with influenza in the first 2 years of life, but the differences were too small to be clinically significant. Ongoing studies are needed to devise strategies to target early influenza vaccination.

Disclosures
S. Rao, GSK: Investigator, Research grant.
987. Repeated Exposure to an Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV): A Randomized, Observer Blind, Multicenter Study
Authors: Daly Wendy , Ramsey Keith , Forsten Aino , Heijnen Esther , Leav Brett , Oberye Janine , Zhang Bin , Pacciarini Filippo , Vesikari Timo 
Published: November 2018

Abstract

Background
The safety, immunogenicity, and efficacy associated with administration of of aQIV in children 6 months through 5 years of age was investigated.1 Although enhanced immunogenicity in children was demonstrated for MF59-adjuvanted influenza vaccines after first administration, the impact of repeated vaccination on immunogenicity and safety has not been evaluated.

Methods
A total of 607 subjects who participated in parent study, now aged 12 months through 6 years, were enrolled the subsequent year and received a single dose of study vaccine. Enrolled subjects received the same type of influenza vaccine administered in the parent study (aQIV or nonadjuvanted comparator). Blood samples were taken for immunogenicity assessment prior to the second year vaccination, and 21 and 180 days after vaccination.

Results
At baseline, approximately 12 months after vaccination in the parent study, subjects in the aQIV group had significantly greater geometric mean titer (GMT) values against all four homologous strains compared with subjects in the nonadjuvanted vaccine group. After year 2 vaccination, CBER criteria for seroconversion and hemagglutination inhibition (HI) titer ≥1:40 were met for the aQIV group for all four homologous strains tested at Day 22. At both Day 22 and Day 181, subjects who received aQIV had significantly greater GMT values for HI against all four homologous strains compared with those who received nonadjuvanted vaccine. Increased immune response of aQIV vs. nonadjuvanted vaccine was also observed for the selected heterologous strains tested at baseline, Day 22 and Day 181. In terms of safety, transient and generally mild to moderate reactogenicity was more commonly observed in the aQIV group vs. the nonadjuvanted group, but overall safety profiles were similar and comparable to the parent study.

Conclusion
This first-year revaccination study in young children confirms enhanced immunogenicity and similar safety profile after repeat aQIV vaccination compared with repeat nonadjuvanted influenza vaccination.
Reference
1.Vesikari T et al. Lancet Respir Med 2018;6:345–356.

Disclosures
K. Ramsey, Seqirus: Investigator, Research support. Novartis: Investigator, Research support. E. Heijnen, Seqirus: Employee and Shareholder, Global Employee Share Plan and Salary. B. Leav, Seqirus: Employee and Shareholder, Salary. J. Oberye, Seqirus: Employee and Shareholder, Global Employee Share Plan and Salary. B. Zhang, Seqirus: Employee and Shareholder, Company stock and Salary. T. Vesikari, Seqirus: Consultant, Consulting fee.
989. Clinical Effectiveness of High-Dose Trivalent vs. Quadrivalent Influenza Vaccination Among Veterans Health Administration Patients
Authors: Young-Xu Yinong , Russo Ellyn , Neupane Nabin , Lewis Melissa , Halchenko Yuliya 
Published: November 2018

Abstract

Background
Despite the widespread availability of several injectable inactivated influenza vaccines (IIV), including the trivalent standard-dose (IIV3-SD) and high-dose (IIV3-HD), and the quadrivalent (IIV4), the US Advisory Committee on Immunization Practices does not currently recommend one over another. The objective of this study was to assess the relative vaccine effectiveness (rVE) of IIV3-HD and IIV4 vs. IIV3-SD.

Methods
rVE was estimated from a retrospective cohort study of Veterans aged 65 years and older who received an IIV during the 2014–2015 influenza season. Veterans Health Administration (VHA) electronic medical records were linked with Centers for Medicare and Medicate Services administrative claims to capture the study outcomes of hospitalizations and baseline characteristics. The inverse probability of treatment weight (IPTW) method was used to adjust for potential confounding due to unmeasured factors associated with IIV3-SD, IIV3-HD, or IIV4 vaccination. The probability was estimated based on patient sociodemographic characteristics, comorbidities, pre-influenza season hospitalizations, prior season influenza vaccination, and use of immunosuppressive medication.

Results
Our study population included 782,346 VHA patients vaccinated during the 2014–2015 season. Of these, 10,543 (1%) received IIV4, while 59,536 (8%) received IIV3-HD and 712,267 (91%) received IIV3-SD. 11,626 (1.5%) were female and 588,324 (76%) were non-Hispanic white. Compared with those that received IIV3-SD vaccine, the IPTW-adjusted rVE for IIV3-HD was 7% (95% CI, 9%–21%) against all-cause, 15% (95% CI, 10%–17%) against cardiorespiratory associated, and 13% (95% CI, 8%–17%) against influenza/pneumonia-associated hospitalization. For those that received IIV4, the IPTW-adjusted rVE was 4% (95% CI, 1%–4%), 1% (95% CI, −2%–5%), and 0% (95% CI, −9%–8%), respectively.

Conclusion
IIV3-HD is more effective than, and IIV4 is as effective as, IIV3-SD vaccination in preventing influenza/pneumonia-associated, cardiorespiratory, and all-cause hospitalizations. Additional studies that employ methods to control for unmeasured confounding are warranted as the use of IIV4 expands.

Disclosures
All authors: No reported disclosures.
997. Protection of Unvaccinated Individuals by Influenza Vaccine Coverage of Household Contacts
Authors: Malosh Ryan E , Evans Richard , Martin Emily T , Petrie Joshua G , Monto Arnold S 
Published: November 2018

Abstract

Background
The evidence that influenza vaccination programs provide some protection to unvaccinated members of a community (i.e., indirect effects) is lacking. We sought to determine the indirect effects of influenza vaccine in prospective cohort study of households with children.

Methods
We used longitudinal data over six influenza seasons from the Household Influenza Vaccine Evaluation (HIVE) study. We categorized households each season based on the proportion of members who received a seasonal influenza vaccination: unvaccinated (0%), low coverage (1–50%), moderate coverage (50–99%), and fully vaccinated (100%). We used mixed-effect Poisson regression models adjusted for age group and sex with random effects to account for household clustering and repeated measures. We estimated the association between the proportion of vaccinated household members and the incidence of influenza virus infection in the entire cohort. We then estimated the indirect effects of influenza vaccination by comparing unvaccinated members of households with low levels of vaccination to unvaccinated members of households with higher levels of vaccination.

Results
During 7,286 person-seasons of follow-up, we detected 578 cases (8 per 100/season) of influenza virus infection. The seasonal incidence rate was highest in completely unvaccinated households (10 per 100/seasons) and lower at all other levels of vaccine coverage (Figure 1). Individuals in fully vaccinated households had a 29% lower seasonal incidence rate of influenza infection compare to those in unvaccinated households (IRR 0.72, 95% CI 0.56–0.93). The estimated indirect VE comparing unvaccinated individuals in completely unvaccinated households to those in households with moderate vaccine coverage was 40 % (95% CI −4 to 65).

Conclusion
We demonstrate that vaccination of close contacts can reduce incidence of influenza in unvaccinated members of a community. Despite insufficient evidence, guidance from public health authorities currently suggests that vaccination protects close contacts. Our findings quantifying the protective effects of seasonal influenza vaccination of household contacts in unvaccinated individuals can provide clearer evidence for global vaccine recommendations.

Disclosures
All authors: No reported disclosures.