bluuebunny/crossref_metadata_2025_split huggingface dataset:
754. Prevalence of Latent Tuberculosis Infection Among Healthcare Workers at a Tertiary Care University Hospital
Authors: Choo Eun Ju , Park Se Yoon 
Published: November 2018

Abstract

Background
We investigated the prevalence of latent tuberculosis infection (LTBI) among healthcare workers (HCWs) and analyzed its risk factors in a tertiary care university hospital in South Korea in a population with intermediate tuberculosis (TB) burden.

Methods
A standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant. QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay and chest radiography were performed to investigate the rate of LTBI.

Results
A total of 1,429 participants, 213 (14.9%) doctors and 988 (69.1%) nurses and 228 (16.0%) others were enrolled. The mean age of the subjects was 33.0 years old, and 1,175 (82.2%) were female. Of the participants, 94.5% had received BCG vaccine. QFT-GIT assays were positive for 156 subjects (10.9%). Of the 213 doctors, 28 (13.1%) were positive by QFT-GIT, and among the 988 nurses, 94 (9.5%) had positive QFT-GIT results. Experience of working in hospital was significantly associated with positive LTBI test results by QFT-GIT assay. Gender and duration of employment as an HCW were significantly associated with having a positive QFT-GIT result in univariate analyses. In multivariate analyses, duration of employment as an HCW (&gt;15 years) (odds ratio, 1.98; 95% confidence interval, 1.14–3.43) was independently associated with increased risk of a positive QFT-GIT result.

Conclusion
A high prevalence of LTBI was found among our HCWs. Considering the association between the experience of working in hospital and high risk of LTBI. The risk for tuberculosis infection among HCWs was higher than general population, which suggests that stricter preventive strategies against nosocomial tuberculosis infection should be implemented.

Disclosures
All authors: No reported disclosures.
759. Molecular Characterization and Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) and Identification of Possible Cases of Local Transmission of MDR-TB in Kuwait
Authors: Mokaddas Eiman , Ahmad Suhail , Al-Mutairi Noura 
Published: November 2018

Abstract

Background
Increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is hampering efforts to control TB. Kuwait is a low (25/100,000) TB incidence country and ~1% of Mycobacterium tuberculosis strains are resistant to rifampin, RIF and isoniazid, INH (MDR-TB). Analysis of resistance conferring mutations in seven genes was combined with spoligotyping for detecting local transmission of MDR-TB in Kuwait.

Methods
MDR-TB strains (n = 131) from 88 TB patients and 50 susceptible strains were used. Susceptibility testing was done by MGIT 960 system, gMTBDRplus assay and PCR-sequencing of three regions of rpoB, katG codon 315 (katG315) + inhA regulatory region, embB (embB306/embB406/embB497 regions), rpsL + rrs-500–900 regions and pncA for RIF, INH, ethambutol (EMB), streptomycin (SM) and pyrazinamide (PZA), respectively. Sequencing data were used to construct phylogenetic tree by MEGA7 software. Spoligotypes were identified by SITVIT2 and phylogenetic tree was made by MIRU-VNTRplus software.

Results
Mutations were detected in most isolates in rpoB, katG+inhA, embB, rpsL+rrs and pncA which confer resistance to RIF, INH, EMB, SM and PZA, respectively. Phylogenetic analysis of multi-locus concatenated sequences showed unique patterns for 51 patient’s isolates while 37 patient’s isolates grouped in 14 clusters. Spoligotyping identified 35 patterns (19 unique patterns and 69 patients’s isolates in 16 patterns) including 11 orphan patterns. Sixteen isolates yielded six clusters (each containing two to five isolates) by both fingerprinting methods.

Conclusion
Our study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified six potential cases of local transmission of MDR-TB involving two to five subjects (including five Kuwaiti patients) which had escaped detection by routine surveillance studies. Prospective detection of resistance conferring mutations thus identifies possible cases of local transmission of MDR-TB in low TB incidence countries.

Disclosures
All authors: No reported disclosures.
764. Impact of Diabetes Mellitus on the Presentation and Response to Treatment of Adults With Pulmonary Tuberculosis in Qatar
Authors: Dousa Khalid M , Hamad Abdelrahman , Alsoub Hussam , Elzouki Abdel-Naser , Alwakeel Mahmoud I , Thiel Bonnie A , Johnson John L 
Published: November 2018

Abstract

Background
Persons with diabetes mellitus (DM) have a 3-fold increased risk of TB. Vitamin D deficiency also is associated with a 4-fold increase in risk of progression of TB from latent TB infection to active TB. Qatar is an oil rich country with high prevalence of diabetes, obesity, and vitamin D deficiency. We aimed to evaluate the effect of diabetes mellitus on manifestations and response to treatment in adults with DM and TB.

Methods
Retrospective national hospital-based study of adult from January 2007 to December 2011, comparing TB-infected patients with and without DM.

Results
Of 134 adults with DM and TB, 62 (47%) became culture negative after 8 weeks of anti-TB treatment compared with 84 (72%) patients without DM. Patients with DM had more frequent lower lobe disease (28% vs. 17%, P = 0.03). Week 8 sputum culture conversion did not differ between patients by the degree of dysglyemia at time of diagnosis and onset of anti-TB treatment (70% vs. 46%, P = 0.09).

Conclusion
Diabetes mellitus was associated with delayed sputum culture conversion at two month and atypical radiological findings in adults with pulmonary TB in Qatar. Glycemic control had no effect on week-8 sputum culture conversion.

Disclosures
All authors: No reported disclosures.
774. Extrapulmonary Tuberculosis: Impact of Early Diagnosis and Treatment on Mortality
Authors: Walayat Saqib , Awwal Talha , Ren Jimna , Farrell John 
Published: November 2018

Abstract

Background
Pakistan has a high burden of endemic Mycobacterium tuberculos is complex (MTC) disease. Extrapulmonary tuberculosis (EPT) is defined as MTC infection involving any part of the body other than the lung. Extrapulmonary tuberculosis (EPT) is seen 20% of MTC infection in Pakistan, diagnosis is often delayed, and timeliness of initiation of treatment is extremely varied. We conducted a retrospective review of all cases of EPT presenting to a large public hospital in Islamabad, Pakistan to identify the role of early diagnosis and clinical treatment on patients with extra pulmonary tuberculosis.

Methods
Retrospective review of EPT diagnosed at Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. All cases diagnosed and treated as EPT from January to June 2016 were included. Demographic, clinical and laboratory data were extracted from PIMS Medical records and TB01 cards from the National TB Control Program Pakistan. All patients were contacted to determine outcome status. Study was approved from National TB control Program.

Results
Two hundred seventy-five patients were identified who received a diagnosis of EPT. Mean age was 34.4 years; ratio of men to woman was 1.3:1. Pleural tuberculosis was the most common site involved (28.7%). The next most frequent site involved was lymphatic disease (20.3%). 47.6 percent of patients (113/275) were diagnosed by clinical criteria alone (i.e., symptoms and radiographic imaging). There were only three cases of culture confirmed EPT in the cohort. The overall cure rate was 82.9%. There was no difference of cure rates between the cure rates of males and females. Diagnosis based on clinical criteria was associated with significantly higher cure rate (87.6% vs. 79.6%, P = 0.038) and lower mortality (5.3% vs. 9.3%, P = 0.041) compared with laboratory-based diagnosis (5.3% vs. 9.3%, respectively). Improved outcomes and mortality benefit was seen in patients who were treated based on clinical criteria as compared with those in whom treatment was delayed due to biochemical confirmation (Odds ratio 0.28, 95% CI: 0.086–0.95). Sixteen cases were lost to follow-up.

Conclusion
Early initiation of treatment based on clinical criteria was associated with lower mortality and overall outcome benefit in our study cohort. However, further larger studies of patients with EPT are required to validate our observations.

Disclosures
All authors: No reported disclosures.
777. Ten-Year Experience of Tertiary Hospital Regarding Epidemiology, Diagnostic Method, and Drug Resistance of Tuberculosis—Jeddah, Saudi Arabia
Authors: Qutub Mohammed , Aldabbagh Yasser , Govindan Prasanth , Alamoudi Ebtihal 
Published: November 2018

Abstract

Background
The prevalence of tuberculosis across Saudi Arabia is variable with western provinces have the highest incidence. This study aimed to determine the epidemiology of tuberculosis in Jeddah, the age and gender distribution and the accuracy of conventional diagnostic method, for better understanding of tuberculosis-resistant pattern in the country.

Methods
Three hundred forty-four culture proven tuberculosis where collected from November 2006 to November 2016 in KFSHRC. AFB smear and nucleic acid amplification test (NAAT) were conducted in all positive cultures, and all data were analyzed using SPSS. Mean days number to culture positivity was 12.79.

Results
TB showed young age predominant (59.5%) compared with older population (37.0%) and pediatrics (3.5%), with 55.4% males and 44.6% females, 54.8% of samples were taken from pulmonary and 45.2% from extra pulmonary site of infection. 68.3% and 5.9% of the tuberculosis proven culture were negative by using AFB smear and NAAT, respectively, and only 68.8% were positive for mycobacterium tuberculosis complex by using NAAT. Resistant level to first-line anti tuberculosis of 12.5%, 10.3%, 5.2%, 2.6%, 1.3%, 2.6% to Streptomycin, isoniazid, pyrazinamide, Rifampicin, Ethambutol and multidrug-resistant, respectively, was observed in our study.

Conclusion
Young age predominance, high values of negative smear and NAAT increased incidence of extra pulmonary site of infection and Re-emergence of tuberculosis resistant which was observed in our study compared with previous national surveys (Illustrated in Figure 1), all should alter physicians’ Attention when investigating patients in Saudi Arabia and high clinical suspicion should be considered.

Disclosures
All authors: No reported disclosures.
778. Trend of Tuberculosis Meningitis and Associated Mortality in Texas, 2010–2017, A Large Population-Based Analysis
Authors: Nguyen Duc T , Agarwal Saroochi , Graviss Edward A 
Published: November 2018

Abstract

Background
As the most severe form of tuberculosis (TB), TB meningitis (TBM) is still associated with high mortality even in developed countries. In certain US states more than 50% of the TBM patients eventually die or have neurological complications despite having advanced healthcare settings. This population-based analysis aimed to determine the risk factors and trends associated with TBM morbidity and mortality using state-wide surveillance data.

Methods
De-identified surveillance data of all confirmed TB patients from the state of Texas reported between January 2010 and December 2017 to the National TB Surveillance System was analyzed. Spatial distribution of TBM cases was presented by Stata’s Geographic Information Systems mapping. Univariate and multiple logistic regression were used to identify risk factors associated with meningitis morbidity and mortality. Non-parametric trend testing was used for the morbidity and mortality trends.

Results
Among 10,103 TB patients reported from Texas between 2010 and 2017, 192 (1.9%) had TBM. Over the 8-year period, TBM proportion fluctuated between 1.5% and 2.7% with peaks in 2011 (2.7%) and 2016 (2.1%) and an overall trend z = −1.32, P = 0.19. TBM had higher mortality at diagnosis (8.9%), during treatment (20.3%) and overall (22.9%) than non-TBM (1.9%, 6.8%, and 7.2%, respectively, P &lt; 0.001). While the mortality during treatment was unchanged overtime in non-TBM patients (z=0.5, P = 0.62), it has consistently increased in TBM patients since 2013 (z=3.09, P = 0.002). TBM patients had more than 7 times the odds for overall death in multivariate analysis [OR 7.25 (95% CI 4.64, 11.33), P &lt; 0.001]. TBM patients were younger, more likely to present with miliary TB or HIV(+). Age ≥45 years, resident of a long-term care facility, IDU, diabetes, chronic kidney disease, abnormal chest radiograph, positive AFB smear or culture, culture not converted from positive to negative, and HIV(+) were independently associated with a higher mortality.

Conclusion
TBM remains a challenge in Texas with significantly higher mortality. Risk factors determined by multivariate modeling will inform health professionals and lay a foundation for the development of more effective strategies for TBM prevention and management.

Disclosures
All authors: No reported disclosures.
785. Treatment of Mycobacterium immunogenum Skin and Soft-Tissue Infections: A Case in a Peritoneal Dialysis Patient
Authors: El-Nahal Walid , Shenoy Abhishek , Walker McCall , Chopra Tushar , Townsend Greg , Heysell Scott , Eby Joshua 
Published: November 2018

Abstract

Background
Mycobacterium immunogenum is a somewhat recently identified species of rapidly growing nontuberculous mycobacteria, genetically related to M. abscessus and M. chelonae. Resistance patterns of rapidly growing nontuberculous mycobacterium species can make them difficult to treat. This is particularly true of M. immunogenum, in part due to the infrequency of reported cases of human infection and limited data to guide therapy.

Methods
We present here a case of M. immunogenum skin and soft-tissue infection at the site of insertion of a peritoneal dialysis catheter in a patient with end-stage renal disease. He initially presented with nodular subcutaneous lesions around his catheter site that progressed through oral antibiotics. This led to sampling which confirmed the diagnosis of M. immunogenum. We conducted a review of the literature to identify previously reported cases of M. immunogenum, including skin and soft-tissue infections, and used these data to guide management.

Results
We reviewed 11 reports (cases and case series) of Mycobacterium immunogenum in the literature. Susceptibilities often take weeks to return, and so empiric therapy is based on case series, and then later adjusted based on susceptibilities. Patients received combined antimicrobial regimens with durations of 2 weeks to 12 months, with variable outcomes. Several required surgical debridement, as was the case with our patient. His PD catheter was removed and he was treated empirically with amikacin, azithromycin, and tigecycline intravenous induction. His ultimate long-term regimen was later switched to azithromycin, clofazimine, and tedizolid due to side effects and the eventually available susceptibility profile.

Conclusion
The treatment of M. immunogenum remains a challenge due to the relative scarcity of data to guide treatment, and consequent lack of systemic approach to therapy. Most reported cases involve the use of a macrolide, often in combination with an aminoglycoside or a fluoroquinolone. Several started with intravenous induction, followed by transition to oral therapy on the order of weeks to months. Others also require surgical debridement. More data are required to develop a standardized approach to the treatment of M. immunogenum.

Disclosures
All authors: No reported disclosures.
788. Therapeutic Drug Monitoring for Pyrazinamide During Tuberculosis Treatment: What Is the Diagnostic Accuracy?
Authors: Anderson Ginger , Vinnard Christopher 
Published: November 2018

Abstract

Background
Pyrazinamide (PZA) is a key drug for both drug-sensitive and drug-resistant tuberculosis (TB). Patients co-infected with TB and human immunodeficiency virus (HIV) are more likely to have low blood levels of PZA, associated with inferior outcomes. Therapeutic drug monitoring (TDM) with sparse blood sampling is recommended for high-risk groups, including HIV/TB patients, but the accuracy is uncertain. We performed a pharmacokinetic (PK) simulation study to estimate the diagnostic accuracy of TDM for PZA among HIV/TB patients.

Methods
We recently performed a population PK study among HIV/TB patients in Botswana, identifying a 1-compartment model with first-order elimination. In the current work, we performed an intensive PK simulation (n = 10,000 patients) to determine the accuracy of sparse blood sampling in identifying HIV/TB patients with low PZA blood levels, as defined by the AUC in a dosing interval (AUC0-24) predictive of successful outcome (363 mg*hr/L). PZA dosing followed WHO guidelines with weight-based dosing bands. In secondary analysis, we examined the peak concentration (Cmax) target predictive of 2-month sputum conversion (58 mg/L). To determine the accuracy of sparse sampling (2- and 6-hours), we performed receiver-operating-characteristic (ROC) analysis, with bootstrapping (n = 1,000) for 95% confidence intervals (CI), and defined accuracy as the area under the ROC curve.

Results
In this simulation PK study of PZA among HIV/TB patients, the PZA AUC0-24 fell below the target in 29% of patients, while in 71% of patients the PZA Cmax was below the target. For the AUC0-24 target, the area under the ROC curve was 0.69 (95% CI 0.68–0.70) for a single 2-hour sample, increasing to 0.75 (95% CI 0.74–0.76) for 2- and 6-hour samples. For the Cmax target, diagnostic accuracy was similar for a 2-hour sample (0.87, 95% CI 0.86–0.87) and 2- and 6-hour samples (0.88, 95% CI 0.88–0.89).

Conclusion
We observed modest diagnostic accuracy of TDM for identifying in silico HIV/TB patients with low PZA AUC0-24, and higher accuracy for low Cmax. By identifying diagnostic performance characteristics of sparse sampling strategies, including optimal cut-offs, the ROC framework can support wider implementation of TDM in high-risk TB populations.

Disclosures
All authors: No reported disclosures.
794. Infectivity of Smear-Positive Pulmonary TB After 2 Weeks of Rifampicin-based Anti-Tuberculous Therapy
Authors: Alhowady Faraj , Elmaki Nada , Ali Maisa , Husain Ahmad , Al-Maslamani Muna , Alsuwaidi Zubaida , Mohamed Mahmoud , Alsoub Hussam 
Published: November 2018

Abstract

Background
Pulmonary tuberculosis (TB) remains one of the leading infectious causes of morbidity and mortality worldwide. Most data showed that infectiousness of pulmonary TB diminishes rapidly after 2 weeks of effective anti-tuberculous therapy and the bacilli seen in the smear after 2 weeks are most likely nonviable. We aim to assess this hypothesis by doing sputum culture after 2 weeks of therapy to assess the viability of the bacilli in the smear.

Methods
A prospective cohort study was conducted on patients admitted to Communicable Disease Centre (CDC), Qatar with smear positive pulmonary tuberculosis during the period November 2013–November 2014. We repeated sputum smear and culture after 2 weeks of rifampicin based regimen to assess the infectivity. Demographic and clinical characteristics of patients was evaluated and compared with smear and culture conversion rate.

Results
Ninety-five cases were included in the study. All had sputum smear and culture after 2 weeks of supervised rifampicin based therapy (Table 1). Sputum culture at two weeks of treatment was positive in 91 cases (95.7%) and only four cases were culture negative after 2 weeks. Demographic and clinical characteristics were compared with the culture status after 2 weeks, found Patient from Indian subcontinent and symptoms duration more than 1 month are less likely to clear infection after 2 weeks with P-value 0.01 and 0.009, respectively (Table 2).

The calculated mean for sputum smear and culture conversion rate was 4 and 8 weeks, respectively. The presence of cough and the duration of symptoms were associated significantly with rapid sputum conversion (P &lt; 0.05); however, the presence of cavity on CXR had no statistical significant effect (Table 3).

Conclusion
Majority of our patients in the study have positive TB culture after two weeks of rifampicin based anti-tuberculosis therapy. So, discontinuation of the isolation after 2 weeks of treatment assuming that bacilli in the smear are nonviable may not be safe.

Disclosures
All authors: No reported disclosures.
803. Overcoming β-Lactam Resistance in Mycobacterium abscessus
Authors: Story-Roller Elizabeth , Lamichhane Gyanu 
Published: November 2018

Abstract

Background
Mycobacterium abscessus (Mab) is an environmentally acquired nontuberculous mycobacterium (NTM) that causes severe pulmonary infections in patients with chronic lung disease, such as cystic fibrosis (CF). The incidence of drug-resistant Mab infections in CF patients in the United States is steadily rising, making it increasingly difficult to manage these often chronic and incurable infections. Mab requires two enzyme classes, l,d- and d,d-transpeptidases, to synthesize peptidoglycan (PG); an integral component of the bacterial cell wall. Each enzyme class is uniquely susceptible to different classes of β-lactam antibiotics. We hypothesize that a combination of two β-lactams, each specific for an enzyme class, will optimally inhibit PG synthesis and swiftly kill Mab, with potential to overcome drug-resistance.

Methods
Paired antibiotic combinations were tested in vitro for synergy against the Mab reference strain ATCC 19977 at 106 CFU/mL, per CLSI guidelines. Combinations included two β-lactams, a β-lactam and a β-lactamase inhibitor, or a β-lactam and a rifamycin. The minimum inhibitory concentration (MIC) of each drug was initially confirmed via broth microdilution assay. A validated checkerboard assay was used to determine the fractional inhibitory concentration index (FICI) for each combination to identify pairs that exhibit synergistic activity against Mab.

Results
Of the initial 227 combinations screened, 18 pairs exhibited a high level of synergy (FICI ≤ 0.5). Half of these were combinations of two β-lactams. The average reduction in MIC for each drug in combination was at least fourfold, with 8/18 combinations exhibiting reductions greater than eightfold. Although MIC breakpoints against Mab have not been established for all of the antibiotics tested in this study, the MICs of at least seven combinations were within the therapeutic range.

Conclusion
Comprehensive inhibition of essential enzymes involved in PG synthesis requires more than one β-lactam antibiotic, and this phenomenon is hypothesized to be the basis for observed synergy between β-lactams. Some of the combinations reduced MICs to within therapeutically achievable levels, potentially leading to vital new treatment options against drug-resistant Mab.

Disclosures
All authors: No reported disclosures.