bluuebunny/crossref_metadata_2025 huggingface dataset:
732. Description of Diagnoses and Antibiotic Management of Otitis Media and Otitis Externa in Adults
Authors: Pontefract Benjamin , Madaras-Kelly Karl , Nevers McKenna , Fleming-Dutra Katherine , Samore Matthew
Published: November 2018

Background

Otitis diagnoses include acute otitis media (AOM), otitis media with effusion (OME), and acute otitis externa (AOE). AOM and OME occur primarily in children, whereas AOE occurs with similar frequency in children and adults. Treatment with amoxicillin or close observation without antibiotics is recommended for pediatric AOM, and oral antibiotics are not routinely recommended to treat OME or uncomplicated AOE. Data on otitis diagnoses in adults is limited. This study’s purpose is to characterize the incidence and antibiotic management of otitis diagnoses in adults. Methods. A retrospective cohort of ambulatory veterans who presented at one of six VA Medical Centers during years 2014–2016 with an ICD-9 or -10 code for AOM, OME, and AOE diagnoses was developed. Data extracted included demographics, vital signs, diagnoses, and antibiotic prescriptions. Incident density rates for adult AOM, OME, and AOE were calculated and compared with rates for acute rhinosinusitis. Antibiotic prescribing rates were calculated. Results. Of 4,759 otitis visits identified, the most frequent diagnoses included AOM (38%), OME (25%), and AOE (34%). A single otitis diagnosis was coded in 95.6% of visits and 13.0% had co-diagnosis of another acute respiratory infection (ARI). The incidence density (±95% confidence interval) was 5.4 (5.2, 5.7), 3.6 (3.5, 3.9), and 4.9 (4.7, 5.2) cases per 1,000 patient-years for AOM, OME, and AOE, respectively. For comparison, the incidence density of rhinosinusitis was 16.6 (16.2, 17.0) cases per 1,000 patient-years. Oral antibiotics were prescribed in 48% of visits: AOM (50%), OME (49%), and AOE (47%). Topical antibiotics were prescribed in 32% of AOE visits. The most common oral and otic antibiotics prescribed were amoxicillin/clavulanate (36%), amoxicillin (28%), azithromycin (11%), and hydrocortisone/neomycin/polymyxin (65%), respectively. Conclusion. Otitis diagnoses in adults were common independent of ARI co-diagnoses, but less frequent than rhinosinusitis. Almost half of the patients received an oral antibiotic including those with AOE and OME, indicating a possible focus for antibiotic stewardship programs. Studies to evaluate diagnostic accuracy and treatment of otitis diagnoses in adults are needed.

Disclosures

All authors: No reported disclosures.
734. Post-exposure Management of Influenza in Roommates at a Tertiary Care Cancer Center
Authors: Carlino Sandra , Kamboj Mini
Published: November 2018

Background

Post-exposure antiviral chemoprophylaxis with neuraminidase inhibitors (NI) is 80% effective in preventing influenza in household members. In hospital settings, management of exposed roommates has not been specifically addressed in clinical studies. Some experts recommend immunocompromised individuals exposed to influenza to receive therapeutic doses of NI as a preventive measure regardless of duration of exposure. The objective of this study was to determine optimal intervention in high-risk patients exposed to influenza based on duration of spatial overlap and viral testing at the time exposure is recognized.

Methods

MSK is a 473-bed tertiary care cancer center. Infection Control performs contact investigation for cases diagnosed with influenza including baseline testing of exposed roommates using a multiplex PCR test. The primary team is notified of exposures and makes recommendations regarding prophylaxis. Retrospective review of patients considered exposed to influenza during three seasons was performed. Information on spatial overlap, prophylaxis, and viral testing was extracted.

Results

Out of 64 patients exposed, five (8%) developed influenza (table). Baseline testing was done in 51 (80%): none with overlap of <4 days were symptomatic or tested positive; 2/12 with overlap >4 days tested positive. Attack rate for those with exposure time <4 days who did not receive prophylaxis was 2.6%. No breakthrough infection occurred in the prophylaxis group. Post exposure follow-up revealed two more cases for those overlapping >4 days; a single case of breakthrough infection developed at 7 days, resistance testing was not performed, and patient responded to therapeutic doses of NI without persistent shedding.

Conclusion

Duration of overlap in semi-private rooms correlates with secondary cases of influenza. Prophylactic doses of NI are safe and effective for asymptomatic individuals with exposure <4 days to index case. For patients with spatial overlap >4 days, baseline testing is recommended to recognize cases early and interrupt nosocomial transmission.

Disclosures

All authors: No reported disclosures.
735. Severity and Healthcare Costs of Respiratory Syncytial Virus Hospitalizations in US Preterm Infants Born at 29–34 Weeks Gestation: 2014–2016
Authors: Goldstein Mitchell , Krilov Leonard R , Fergie Jaime , Ambrose Christopher S , Wade Sally , Kong Amanda , Brannman Lance
Published: November 2018

Background

In 2014, the American Academy of Pediatrics recommended against the use of respiratory syncytial virus (RSV) immunoprophylaxis in infants 29–34 weeks gestational age (wGA) at birth without chronic lung disease/bronchopulmonary dysplasia (CLD/BPD) or congenital heart disease (CHD). To inform discussions of the clinical and economic value of RSV immunoprophylaxis in these infants, we compared RSV hospitalization (RSVH) severity and costs incurred by infants hospitalized from 2014–2016 at <6 months chronologic age (CA) for two groups: 29–34 wGA infants without CLD/BPD or CHD and term infants (≥37 wGA) without major health problems.

Methods

Births were identified in the MarketScan Commercial (COM) and Multistate Medicaid (MED) databases. Term and 29–34 wGA infants without CLD/BPD or CHD were selected using DRG and ICD-9/10-CM diagnosis codes. RSVH occurring from Julu 1, 2014 to June 30, 2016 while infants were <6 months CA (the period of highest RSVH incidence) were identified by ICD-9/10-CM diagnosis codes. Severity measures were length of stay (LOS) in days, intensive care unit (ICU) admissions, and healthcare costs (paid amounts on reimbursed hospital claims in 2016 US$). Comparisons between term and 29–34 wGA infants were made with t-tests and chi-squared tests.

Results

There were 1,114 RSVH in the COM data and 3,167 RSVH in the MED data during the study period. Mean LOS was longer for 29–34 wGA infants than term infants for each age category (P < 0.05) and tended to be longer for MED infants vs. COM infants (Figure 1). Thirty-eight percent of COM 29–34 wGA infants and 52% of MED 29–34 wGA infants hospitalized for RSV at <3 months CA were admitted to the ICU (Figure 2). RSVH costs for 29–34 wGA infants were greater than term RSVH costs for each age category (P < 0.05) and were greatest among 29–34 wGA infants hospitalized at <3 months CA: $41,104 for 29–34 wGA COM infants and $24,049 for 29–34 wGA MED infants (Figure 3).

Conclusion

RSVH severity and costs were significantly higher for 29–34 wGA infants without CLD/BPD or CHD relative to term infants. Infants hospitalized at <3 months CA experienced the most severe hospitalizations and incurred the highest costs.

This study was 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. C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks. S. Wade, Wade Outcomes Research and Consulting: Employee, Salary. A. Kong, Truven Health Analytics, an IBM Company: Employee, Salary. L. Brannman, AstraZeneca: Employee, Salary and Stocks.
737. The Prevalence of Diagnosed Chronic Lung Disease in US Infants by Gestational Age: Implications for RSV Policy
Authors: Ambrose Christopher S , Jiang Xiaohui , Mavunda Kunjana
Published: November 2018

Background

Perinatal chronic lung disease (CLD), previously referred to as bronchopulmonary dysplasia (BPD), is associated with preterm birth and occurs rarely among term infants. Children with CLD are at elevated risk for severe RSV disease in the first 2 years of life. Definitions of CLD/BPD identify infants who require supplemental oxygen at 28 days of life or 36 weeks postmenstrual age, with no restriction by gestational age (GA) at birth. However, the AAP Committee on Infectious Disease guidance does not recommend RSV immunoprophylaxis for infants with CLD born at ≥32 weeks gestational age (wGA), even though infants with CLD/BPD up to 41 wGA were included in pivotal efficacy studies. This study determined the prevalence of diagnosed CLD in US infants as a function of wGA at birth and the number of infants with CLD born at ≥32 wGA.

Methods

The Kids’ Inpatient Database (KID) is a nationally representative survey conducted every 3 years in the United States. Birth hospitalization data from KID were utilized to estimate the prevalence of CLD (ICD-9 = 770.7) among US infants in 2003–2012 overall and as a function of coincident codes for GA (ICD-9 = 765.21–765.29, reported in 2-week intervals). The prevalence of CLD among 32 wGA infants was imputed based on the distribution of CLD cases as a function of wGA. KID data from 2015 were not available due to the transition to ICD-10 coding.

Results

A total of 31,984 infants had a CLD diagnosis across the 4 years, representing 0.2% of US births. The prevalence of CLD declined from 20.8 to 19.5 per 10,000 between 2003 and 2012. Of those, 25,554 infants with CLD (80%) had GA coded in the database. The percentage of CLD infants born at <27 wGA increased from 44% in 2003 to 52% in 2012, whereas the percentage at ≥29 wGA decreased from 27% to 21% (figure). Overall, the percentages born at 31–32, 33–34, and >34 wGA were 5.7%, 2.2%, and 1.2%, respectively. An estimated 5.7% of infants with CLD were born at ≥32 wGA, representing 0.9 of every 10,000 US births or ~350 infants annually.

Conclusion

Fewer than 400 infants are born at ≥32 wGA and diagnosed with CLD annually in the United States. The rationale for excluding this small but high-risk group of infants from the population recommended for RSV immunoprophylaxis is not clear.

Funded by AstraZeneca

:Disclosures. C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks. X. Jiang, EpiStat Institute: Employee, Consulting fee and Salary. AstraZeneca: Consultant, Consulting fee. K. Mavunda, AstraZeneca: Speaker’s Bureau, Speaker honorarium.
739. Middle East Respiratory Syndrome Coronavirus Infection Profile in Qatar: A 7-Year Retrospective Study
Authors: Elmaki Nada , Abid Fatma Ben , Farag Elmubasher , Alsoub Hussam , Ghazouani Hafedh Ghazouani , Saleh Mulham Mohed , Dousa Khalid M , Al-Khal Abdullatif , Hashim Samar Mahmoud A , Al- Maslamani Muna
Published: November 2018

Background

A deadly zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) had emerged over the last 7 years in the Arabian Peninsula. As of February 28, 2018, 2,182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide. The objectives of this study were to identify the clinical and epidemiological characteristics of MERS-CoV infection as well as determine its clinical outcome.

Methods

This was a retrospective-observational study of all laboratory confirmed cases of MERS-CoV infection conducted at the main seven hospitals in the State of Qatar from January, 2012 to April 2018. We used the Fast Track diagnostics real-time reverse-transcription polymerase chain reaction (rRT-PCR), targeting the upE and ORF1a genes respectively. Demographics, clinical information, potential contacts and probable risk factors were collected and analyzed by standard statistical methods.

Results

The mean annual incidence was 1.7 per 100,0000 person-years. Among the 24 confirmed cases of of MERS-CoV, males constituted the vast majority of cases (23 males) with a median age of 52 years (range 22–74). Fifty percent of the cases were Qatari and 42% reside in the same region. 67% of the cases had contact with camels, and 21% had contact with MERS-CoV-infected patient. Thirty-eight had travel history within 2 weeks of symptoms onset to the Kingdom of Saudi Arabia. Fifty percent were smokers and 42% had comorbidities.

The median symptoms duration was 4.5 days. Most of the patient presented with flu-like symptoms, were fever was the most common presentation, followed by cough, SOB, diarrhea, abdominal pain and headache, 96%, 83%, 33%, 8%, 8% and 4%, respectively. All patients were admitted to a tertiary hospital with a median hospital stay 41 days (8–97). Forty-five percent patients developed severe sepsis with multi-organ failure and needed ICU admission. Fifty percent patients developed acute kidney injury, 29% patients were on hemodialysis and 16% needed extra-corporeal membrane oxygenation. Thirty-three percent patients died. The rest of patients had recovered from the infection and discharged home. Among those who died all had one or more comorbidities.

Conclusion

MERS-CoV infection is a rare infection in the State of Qatar, seen in both Qataris and expatriates with and without travel history. The infection in patients with comorbidities carries high mortality.

Disclosures

All authors: No reported disclosures.
741. Impact of Adenovirus Co-detections on Illness Severity
Authors: Probst Varvara , Piya Bhinnata , Stewart Laura , Gerber Susan , Rha Brian , Yu Joana , Das Suman , Campbell Angela P , Williams John V , Halasa Natasha B
Published: November 2018

Background

Human adenovirus (AdV) is a common pathogen among children with acute respiratory illnesses (ARI) and is often associated with co-detection with other respiratory viral pathogens. We sought to compare demographic and clinical characteristics in children with ARI who had single-AdV vs. AdV-co-detection with other viruses.

Methods

Children <18 years with fever and/or ARI were enrolled in Vanderbilt Children’s Hospital inpatient setting from 2015 to 2018 and emergency department from 2016 to 2018. Interviews were conducted using standardized case report forms. Nose and throat swab specimens were collected and tested by RT-qPCR for common respiratory pathogens (AdV, RSV, HRV, hMPV, PIV1–4 and Influenza).

Results

Of 2,740 ARI cases, 174 were positive for AdV [88 (51%) single detection], with 53% male, 47% White, 36% Black, 30% Hispanic and median age of 17.2 months. Co-detected pathogens in AdV-positive specimens were RSV(15%), HRV(14%), influenza(5%), PIV1(1%), PIV2(0.6%), PIV3(1.7%), and PIV4(0.6%), hMPV(3%), >1 co-pathogens(9%). Subjects with single-AdV detection were more likely to have an underlying medical condition (42% vs. 24%, P < 0.05). Table 1 compares clinical presentation and severity of single-AdV and AdV-co-detection cases.

Conclusion

Patients with single-AdV detection were less likely to present with ARI symptoms and require oxygen, but were more likely to have underlying medical conditions compared with AdV-co-detection. Further studies to type AdV isolates will help elucidate the role of specific adenovirus types associated with co-detections and illness severity and inform epidemiological information for future vaccine initiatives.

Disclosures

J. V. Williams, Quidel: Board Member, Consulting fee. GlaxoSmithKline: Consultant, Consulting fee. N. B. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.
753. Screening for Latent Mycobacterium tuberculosis Infection (LTBI): A Clinical Conundrum of Public Health Concern
Authors: Bricker Lauren , Brock Jeff , Tippett Jan , Rice Casey , Wittmer Jason , Crippen Alicia , Vemuri Ravi
Published: November 2018

Background

Tumor necrosis factor (TNF)-α inhibitors increase the risk of reactivating LTBI, hence screening is crucial prior to starting therapy. There is a lack of evidence to support a preferred screening regimen in this population, and either tuberculin skin tests (TST) or interferon-γ release assays (IGRAs) are acceptable. Although difficult to assess, the sensitivity of IGRAs and TST are similar (80–95%), while IGRAs are considered to be more specific.

Methods

A 48-year-old White female in rural Iowa with a 30-year history of Crohn’s disease was evaluated for TNF inhibitor therapy. She had no known risk factors for LTBI and was screened using an IGRA which yielded an indeterminate result. A repeat IGRA and a two-step TST were both negative. Subsequently, adalimumab was initiated. Adalimumab was discontinued after 9 months due to progression of Crohn’s, and the patient underwent bowel surgery at a California hospital. Her course was complicated by bilateral pleural effusions requiring thoracentesis twice.

Results

The patient presented 1 month later with upper lobe infiltrative changes and mediastinal adenopathy. A third IGRA was performed and was non-reactive. A bronchoscopy with biopsy was then performed. The next day her dyspnea, cough and fevers worsened. She was admitted to an Iowa hospital where she was immediately put in airborne precautions. Her bronchoalveolar lavage acid-fast bacilli (AFB) smear was 4+, and an induced sputum showed 3+ AFB. Standard TB treatment was initiated. At least 59 patients (17 immunocompromised) and five employees in a private office and 13 employees at the Iowa hospital were exposed, in addition to an unknown number in California.

Conclusion

Although rare, there appears to be a risk for patients on TNF inhibitors who have multiple negative screening tests to become infected with TB. It is unclear whether this represents reactivation of undetected LTBI or new infection, although new TB cases are less likely in rural Iowa where the incidence is 1.53 per 100,000. Patients should be counseled to report any pulmonary symptoms to providers. As demonstrated by this case, airborne precautions should be implemented as soon as possible if clinical suspicion of TB is high despite negative screening tests to reduce exposure to others.

Disclosures

All authors: No reported disclosures.
757. Community Prevalence of Bacteriologically Confirmed Pulmonary Tuberculosis: A 7-Year Retrospective Study
Authors: Sethuraman Nandini , Thirunarayan M a , Subbulakshmi R , Lakshmisree V , Balasubramanian Udhaya
Published: November 2018

Background

It is estimated that about 40% of the Indian population is infected with Mycobacterium tuberculosis (TB), the vast majority of whom have latent TB. However, asymptomatic pulmonary carriage of the TB bacteria contributes to sustenance of the disease in the community and subsequent transmission. The present study was carried out to see the prevalence of culture positive pulmonary tuberculosis in apparently asymptomatic individuals from the community.

Methods

The study population consisted of individuals wishing to migrate to the USA/UK/Canada/Australia and submitting for the mandatory health check prior to obtaining the Visa. Chest X-ray was the initial screening test for diagnosis of tuberculosis. Individuals with any X-ray abnormalities were directed to submit three sputum samples for microscopy and culture which was done on automated culture systems (BacTALERT and MGIT). First-line drug susceptibility (INH, Rifampicin, Pyrazinamide, Ethambutol, Streptomycin) testing data were retrieved wherever available. Data were obtained for a period of 7 years from August 2010 to July 2017.

Results

A total of 140,499 individuals presented for the health check. Of these, 1,002 (0.7%) were further investigated using sputum microscopy and culture based on chest X-ray findings. Of these, 42 (0.4%) individuals were sputum culture positive for Mycobacterium tuberculosis. Except two, none had any respiratory complaints. Eleven (27.5%) of them were smear positive for acid fast bacilli. Most of the patients (30%) belonged to the age group of 18–25 years. Eighty-four percent had no prior history of tuberculosis or treatment for TB. Fifty-nine percent isolates were sensitive to all first-line drugs (Isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin). Twenty-seven percent were resistant to pyrazinamide alone. Fourteen percent were resistant to more than one first-line drug. There were no cases of multidrug resistance.

Conclusion

This is a unique large-scale study which assesses prevalence of culture positive pulmonary tuberculosis in the urban Indian community. It stresses the need for more stringent public health measures to curb transmission of the disease in such a high endemic region such as India.

Disclosures

All authors: No reported disclosures.
758. Tuberculosis Recurrence in New York City: A Retrospective Study
Authors: McPherson Tristan , Trieu Lisa , Meissner Jeanne Sullivan , Ahuja Shama , Burzynski Joseph
Published: November 2018

Background

Tuberculosis (TB) recurrence has been difficult to determine due to diverse definitions. Without knowledge of recurrence rates or associated risk factors, patients with highest likelihood of recurrence may not be identified, contributing to continued morbidity and disease transmission. We aimed to determine the recurrence rate for TB cases, associated clinical findings and patient characteristics.

Methods

We conducted a retrospective study evaluating 7,755 New York City TB cases from 2005 to 2014 for recurrence after appropriate treatment completion through 2017. Demographic, clinical, drug susceptibility testing (DST), and genotype data were collected during routine care. Adjusted odds ratios (aOR) were calculated to estimate associated risk factors for recurrence.

Results

A total of 73 cases were identified with ≥ one recurrence, a rate of 0.9%. Median time to recurrence after treatment was 516 days (IQR 165–1,256). In univariate analysis, pulmonary or combination of pulmonary and extrapulmonary disease, human immunodeficiency virus (HIV) infection, culture positive disease, alcohol abuse, intravenous drug use, and homelessness in the 12 months prior to diagnosis were associated with recurrence (P < 0.05). In adjusted analysis, HIV infection (aOR 2.04 95% CI 1.13–3.67), pulmonary disease (aOR 9.03 95% CI 2.19–37.12), and having both pulmonary and extrapulmonary disease (aOR 17.19 95% CI 4.0–74.0) were independently associated with recurrence. Of 67 cases with positive culture and DST, 10 had additional drug resistance and 14 had new disease sites. Among 36 cases with complete genotyping information, data suggested relapse in 27 (75%) cases and re-infection in two (5.5%). Re-infection could not be ruled out in seven (19%) cases.

Conclusion

The recurrence rate for this period was lower than expected compared with other studies. HIV infection continues to be associated with recurrence despite availability of effective antiviral medication. Those with pulmonary or disseminated TB were more likely to have recurrence compared with only extrapulmonary TB. A notable number of recurrent cases demonstrated new drug resistance or disease manifestations, which should be considered in later treatment regimens and follow-up evaluation.

Disclosures

All authors: No reported disclosures.
760. The Diversity of Mycobacterium tuberculosis in India Is Underestimated and Underreported
Authors: Poonawala Husain , Verma Amit , Kumar Narender
Published: November 2018

Background

The seven lineages of Mycobacterium tuberculosis differ in virulence, transmissibility, drug resistance, and immune responses. We reviewed spoligotype data published from India to determine the distribution and diversity of TB lineages in India.

Methods

Spoligoytpe patterns were extracted from studies published from India and compared against the SpolSimilarity database to determine Spoligotype International Type (SIT) number, sub-lineage and lineage. Minimum spanning trees (MSTs) were created with Phyloviz.

Results

Thirty-four studies list 1,473 spoligotypes containing 8,242 isolates (Table 1), with 6,733 isolates belonging to 472 SITs. Of the remaining 1,001 patterns (1,509 isolates), 351 patterns (491 isolates) match orphans, while 650 patterns (1,018 isolates) are unreported; these 1,509 isolates could potentially form 532 new SITs and 469 orphans. The most common SITs are SIT11 (Lineage 1; 1,218 isolates, 14.78%), SIT26 (Lineage 3; 982,11.91%) and SIT1 (Lineage 2; 618, 7.5%). Figure 1 demonstrates regional differences in lineage distribution. Figure 2 is an MST of all isolates by lineage (“not assigned” are known SITs with no lineage and “unknowns” are previously unreported patterns). Figure 3 is an MST by superfamily, “others” referring to patterns with no known superfamily.

Conclusion

Lineages 1 and 3 dominate in India, in contrast to lineages 2 and 4 prevalent worldwide. The 1,473 SITs reflect the significant diversity of M. tuberculosis in India; the 1,001 orphan and previously unreported patterns suggest this diversity is underestimated. Understanding M. tuberculosis diversity is necessary for clinical and public health interventions to control India’s TB epidemic.

Disclosures

All authors: No reported disclosures.
762. Sex Differences in the Epidemiology of Tuberculosis in Tunisia
Authors: Jemaa Maissa Ben , Koubaa Makram , Ayed Houda Ben , Marrakchi Chakib , Trigui Maroua , Dammak Jamel , Jemaa Mounir Ben
Published: November 2018

Background

According to WHO, many more men than women are diagnosed with tuberculosis (TB) and die from it globally. In light of this fact, examining the gender differences among patients with TB is important to institute effective prevention, coverage and treatment. We aim to study sex differences in the epidemiology and clinical specificities of TB.

Methods

We conducted a retrospective study of patients with TB, of all ages between January 1995 and December 2016. Data were collected from the regional register of tuberculosis implanted at the anti tuberculosis center ATC of Sfax, Southern Sfax.

Results

We recorded 2,771 new cases of TB. Sex ratio was 1.2. Pulmonary Tuberculosis (PT) represented 40.5% of all cases of TB (n = 1,121) and was 2.5 times more frequent in men than women (50.3% vs. 28.7%; P < 0.001). The sex ratio for extra-pulmonary tuberculosis (EPT) was 0.83. Lymph node and abdominal TB were significantly more frequent in women with respectively 52.5% (vs. 37.4%; P < 0.001) and 12.6% (vs. 9.1%; P = 0.025). Pleural and urogenital TB were significantly more common in men (20.3% vs. 8.9%; P < 0.001 and 13.4% vs. 9.8%; P = 0.023 respectively). We did not found any gender differences in other EPT forms. Between 1995 and 2016, overall TB (P = 0.001; rho = 0.64), EPT (P = 0.02; rho = 0.63) and PT (P = 0.03; rho = 0.46) cases were increasingly notified in women while they were stable in men. Death rates were significantly more important in men (3.5 vs. 2.1; P = 0.02). Women experienced recovery more frequently (89.2% vs. 86.7%; P = 0.04) and duration of treatment was significantly higher in women (9 months vs. 8 months; P < 0.001).

Conclusion

Our study highlighted sex differences of TB in the region of Sfax with a higher burden and morbidity in men. National TB programs should actively focus in these results with more routine diagnostic and screening.

Disclosures

All authors: No reported disclosures.
769. An Outbreak of Multidrug-Resistant Tuberculosis, Minnesota 2016–2017
Authors: Desilva Malini , Moore Nora , Thai Dzung , Grimm Mary Beth , Sabuwala Nadya , Brueshaber Milayna , Gordon Sarah , Andersen Laura , Hall Victoria , Buuck Sean , Hickman Cynthia , Stinebaugh Katie , Silk Benjamin , Raz Kayla , Talarico Sarah , Wortham Jonathan , Kingdon Elisabeth , Pistulka Gina , Guerard Krissie , Cowan Lauren , Posey James E , Snippes Vagnone Paula M , McCullough Joel , Tsukayama Dean , Mody Rajal K , Ehresmann Kristen
Published: November 2018

Background

Multidrug-resistant tuberculosis (MDR TB) is more difficult to treat and outcomes are worse than for drug-susceptible TB disease. MDR TB cases in Minnesota increased from zero in 2015 to nine in 2016. Case investigations suggested an outbreak. We describe the public health response, challenges of contact investigations (CIs), and ongoing management of contacts.

Methods

CDC performed whole-genome sequencing (WGS) to evaluate relatedness of MDR TB isolates. We conducted CIs for infectious cases. We created outbreak specific guidelines for screening and management of contacts, and partnered with various agencies to increase MDR TB awareness.

Results

WGS results were consistent with an MDR TB outbreak that included 10 cases (70% pulmonary) as of April 2018. Limited provider awareness about TB contributed to delayed diagnoses. CIs identified 588 contacts; 8.7% (n = 51) of contacts had previously documented positive TB infection test results, and 14% (n = 74) were newly positive for TB infection (median age: 72 years). Eight cases were epidemiologically linked to one Hmong adult day center. Sixty-two contacts started a fluoroquinolone for latent MDR TB infection. Contacts who declined treatment began a 2-year clinical monitoring program.

Conclusion

In this outbreak, delayed diagnoses resulted in long infectious periods and hundreds of contacts. WGS results were consistent with recent transmission. We discovered adult day centers are an overlooked congregate setting. CIs were complicated by limited public health funding and high underlying TB infection prevalence in the affected community. Increased community and provider awareness and intensified screening of contacts resulted in additional case finding and prevention interventions.

Disclosures

All authors: No reported disclosures.
770. Multi-Drug-Resistant Tuberculosis Cases in Arkansas in 2017: A Tale of Two Threats
Authors: Weldon Emily , Patil Naveen , Voyles Jan , Chai Sandra , Majors Marsha , Mukasa Leonard
Published: November 2018

Background

Multi-drug-resistant tuberculosis (MDR-TB) is a threat to TB elimination strategies worldwide. From 1998 to 2016, six cases of MDR-TB were reported in Arkansas. In 2017 alone, three cases were detected. We sought to describe the characteristics of these cases to inform our MDR-TB prevention strategy in AR.

Methods

The surveillance database identified three MDR-TB cases in 2017. A detailed review was done to define the demographics, clinical presentation, and laboratory reports relating to drug susceptibility testing (DST), including molecular detection of drug resistance (MDDR). A search was done in the Genotyping database for genotype patterns of the patient isolates.

Results

All three cases were born outside the United States and developed active disease after arrival in AR. Case 1, age 52, was born in the Marshall Islands, arrived in 2016, and had a history of Type 2 diabetes. He developed MDR-TB in February 2017. Case 2, age 42, was born in Mexico, arrived over 20 years ago, and was HIV positive. He developed TB in July 2016 with a pan-sensitive organism and completed an intermittent treatment regimen. A second TB episode with matching genotype but different drug sensitivities occurred in April 2017, less than 4 months after treatment completion, and was considered treatment failure. Case 3, age 56, was born in the Philippines, arrived in 1990, and was reportedly treated for latent TB infection in 1993 with 6 months of isoniazid. She visited the Philippines April–May 2017 and developed MDR-TB in October 2017. Her isolate was in cluster with a case in Oklahoma who came from Mexico in 2006 and was admitted in an AR hospital with a pan-sensitive organism. There are no epidemiological links between the two cases; only one isolate in each case. Because both isolates were identified in AR State TB laboratory, a complex contamination has been considered with no definite resolution at this time.

Conclusion

MDR-TB, due to both primary and secondary drug resistance, remains a threat in AR. Cooperation and communication between all levels of healthcare are crucial to avoid delayed diagnosis of MDR-TB. Timely DST via technologies like GeneXpert and MDDR service at CDC is critical. Consultation from Centers of Excellence is vital in the treatment of MDR-TB complicated by diabetes and HIV. Whole-genome sequencing could provide clarity in the cluster with discordant DST patterns.

Disclosures

All authors: No reported disclosures.
771. Drug Resistance Tuberculosis (DR-TB), Comorbidities and Risk Factors Identified in a Prospective Multicenter Cohort Study in Indonesia
Authors: Burhan Erlina , Wibisono Banteng , Indah Retna , Sajinadiyasa Gede Ketut , Riyanto Bambang , Kusmiati Tutik , Susanto Nugroho
Published: November 2018

Background

The numbers of patients with drug resistance TB (DR-TB) increased annually by over 20% globally in the last decade. However, data on the prevalence of DR-TB in Indonesia are limited. The objective of this study to estimate the proportion of DR-TB in new and previously treated TB cases, and to identify comorbidities and risk factors.

Methods

This study has been conducted at seven hospitals throughout Indonesia since March 2017. Clinically TB patients ≥18-year-old were enrolled and followed until 6 months after treatment completed. Demography and clinical data were recorded; sputum, blood, urine, and PBMC were collected at several time points. AFB smear, sputum culture, Xpert MTB/RIF, and drug sensitivity tests were performed. Drug resistance TB is determined by Xpert MTB/RIF.

Results

Of 151 enrolled patients, 103 (68%) were confirmed M. tuberculosis by Xpert MTB/RIF, and 47 (46%) were confirmed rifampicin resistance. The distribution of DR-TB in each study site is shown in Figure 1. Among those with comorbidities (38%), comorbidity with diabetes (based on HbA1c level and diabetes history), HIV, and cancer was 9%, 26%, and 7%. Demography, nutrition status, contact and treatment history, and comorbidities are shown in Table 1. DR-TB primary infection contributes to 23% of DR-TB cases. Biomarkers that may predict treatment failure and TB-genotyping are underway.

Conclusion

The proportion of DR-TB in both new and previously treated patients in our cohort was significantly higher than the estimated number from the WHO and Ministry of Health. TB is a serious threat for public health and mitigation plan must be implemented at all levels.

Disclosures

All authors: No reported disclosures.
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

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

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

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 < 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

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 < 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

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

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.