bluuebunny/crossref_metadata_2025 huggingface dataset:
Selected CNS Outcomes Among INSTI Antiretrovirals
Authors: Wohl David , Mills Anthony , Mera Robertino , Piontkowsky David
Published: October 2017

Background

Higher rates of neuropsychiatric events among patients on dolutegravir (DTG) compared with other integrase inhibitors (INSTIs) have been reported from clinic cohorts and one blinded trial. We compared select neurological and psychiatric events in a large sample of patients treated with different INSTIs.

Methods

The Quintiles IMS database, which includes pharmacy and medical claims records, was examined for HIV infected patients treated from 2006 to 2016 with DTG (TIVICAY/TRIUMEQ), elvitegravir (EVG, STRIBILD), or raltegravir (RAL, ISENTRESS). The dependent variable outcomes were insomnia/sleep disturbance and depression. A propensity score was created to adjust for variables associated with treatment with a particular INSTI including age, gender, year of initial INSTI exposure, and enrollment time. Multivariate Poisson mixed models were used to generate incidence rate ratios (IRRs).

Results

Records for 54,151 distinct HIV-infected patients treated with DTG, EVG, or RAL were identified. In the multivariate model the rate of insomnia/sleep disturbance events was significantly higher for patients treated with DTG vs. EVG (IRR 1.21 [95% CI 1.09–1.33, P < 0.001]), but was not significantly different when comparing DTG to RAL (IRR 1.04 [95% CI 0.94–1.14, P = 0.459]). Likewise, the rate of incident depression was significantly higher for patients treated with DTG vs. EVG (IRR 1.18 [95% CI 1.09–1.27, P < 0.001], but not when comparing DTG to RAL (IRR 0.93 [95% CI 0.87 – 1.01, P = 0.068]).

Conclusion

In this analysis using a large healthcare database, significantly higher adjusted rates of both incident insomnia/sleep disturbances (21% more) and depression (18% more) were found among patients treated with DTG compared with EVG. In contrast, a significant difference in the rates of either outcome was not observed when comparing DTG and RAL. Further studies are warranted to determine the risk of neuropsychiatric events in patients treated with different INSTIs.

Disclosures

D. Wohl, Gilead Sciences: Consultant and Investigator, Consulting fee and Research grant; Viiv: Consultant and Investigator, Consulting fee and Research grant; Janssen: Consultant, Consulting fee; Bristol-Myers Squibb: Consultant, Consulting fee; A. Mills, Gilead Sciences: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Viiv: Consultant and Investigator, Consulting fee and Research grant; Merck: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Janssen: Investigator, Research grant; Bristol-Myers Squibb: Investigator, Research grant; Sangamo Bio Sciences: Investigator, Research grant; R. Mera, Gilead Sciences: Employee and Shareholder, Salary; D. Piontkowsky, Gilead Sciences: Employee and Shareholder, Salary
The Impact of active surveillance culture and decolonization programs on NICU MRSA transmission: A multicenter, mechanistic modeling approach.
Authors: Pierce Rebecca , Elward Alexis , Bryant Kristina , Lessler Justin , Milstone Aaron M
Published: October 2017

Background

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major threat to patient safety in the neonatal intensive care unit (NICU). The aim of this study was to assess the effectiveness of active surveillance cultures (ASC) and decolonization in reducing MRSA transmission in the NICU.

Methods

Retrospective cohort data, including admission and discharge times, weekly surveillance culture results and mupirocin-administration information, were collected from three urban, tertiary care NICU in the US. The study period was 2007–2014, during which ASC and decolonization strategies were employed for MRSA control. We used Markov-Chain Monte Carlo methods to fit a probabilistic transmission model to the data. To account for the interval-censored nature of weekly surveillance screening, we used an integrated Bayesian framework to impute the date of conversion to MRSA-positive. We estimated the risk of MRSA acquisition associated with non-patient sources, undetected MRSA carriers, detected MRSA carriers on contact precautions, and MRSA carriers on contact precautions that also received decolonization treatment.

Results

Of the 12,677 neonates that were screened for MRSA colonization at study sites, 533 (4.2%) had a MRSA-positive surveillance culture. Neonates with undetected MRSA colonization were estimated to be the source of 67% (95% credible interval [CI]: 0.64–0.69) of MRSA acquisition. Compared with undetected MRSA carriers, detection and placement on contact precautions deceased the odds of transmission by 99.8% (odds ratio [OR]: 0.0016, 95% CI: 0.0000026–0.033), 99.6% (OR = 0.0036, 95% CI: 0.0000025–0.13), and 99.8% (OR = 0.0024; 95% CI: 0.00000042–0.043) at sites A, B, C, respectively. A 99.9% reduction in transmissibility was sustained among MRSA carriers who also received decolonization treatment (OR = 0.0014, 95% CI: 0.0000080–0.024).

Conclusion

In this multi-centered NICU cohort, ASC and decolonization programs were highly effective in reducing transmission risk from MRSA carriers. Detection of MRSA carriers and the use of contact precautions, alone, were associated with a near-complete reduction in transmission risk. Improving time-to-detection as well as prioritizing nonpatient reservoirs of MRSA could further reduce MRSA acquisition in the NICU.

Disclosures

All authors: No reported disclosures.
Role of M Cells in Human Mucosal Immunity to Mycobacterium tuberculosis
Authors: Nair Vidhya , Khan Haaris , Mitchell Ron , Shiloh Michael U
Published: October 2017

Background

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a bacterial pathogen that infects roughly one-third of the worldÕs population and causes 1–2 million deaths per year. The current paradigm is that phagocytosis of Mtb by patrolling alveolar macrophages initiates Mtb infection. While this model can account for pulmonary TB, it does not adequately explain the occurrence of extrapulmonary forms of TB that manifest in the absence of obvious lung involvement, such as tuberculous cervical lymphadenitis, also known as scrofula. We hypothesized that specialized epithelial cells called microfold cells (M cells) may be an alternate portal of entry for Mtb. Previously we demonstrated that Mtb is able to transcytose across an epithelial barrier in an M cell dependent manner and that M cell mediated transcytosis is vital for Mtb pathogenesis in a mouse model of tuberculosis.

Methods

We used an in vitro M-cell mediated translocation assay and a Mtb mutant lacking a key virulence factor, ESAT6. We used biochemistry and genetics to identify a novel receptor for ESAT6. We also developed a novel explanted human adenoid Mtb infection model to study mucosal immunity.

Results

We now demonstrate that the Mtb virulence factor ESAT6 is necessary and sufficient to mediate binding and transcytosis by M cells in vitro and in vivo, and that uptake of Mtb by M cells requires a unique cell surface ESAT6 receptor. We developed a novel explanted human adenoid model of M cell biology and demonstrate rapid Mtb transcytosis by primary human tissue within 60–120 minutes. Using flow cytometry we find that Mtb is first ingested by M cells and then after transcytosis, by tissue resident antigen-presenting cells. Explanted adenoids from 10 independent donors display a wide range of Mtb uptake.

Conclusion

We conclude that Mtb ESAT6 is necessary for Mtb uptake by M-cells and that binding and transcytosis require a host receptor. Because explanted adenoids display a wide range of Mtb uptake, M cell mediated transcytosis may confer differential susceptibility to scrofula and disseminated disease. These findings are significant as M cells could potentially serve as the basis for novel therapeutic targets against primary Mtb infection.

Disclosures

All authors: No reported disclosures.
Wide Range of Carbapenem-resistant Enterobacteriaceae Incidence and Trends in Emerging Infections Program Surveillance, 2012–2015
Authors: Duffy Nadezhda , Brown Cedric J , Bulens Sandra N , Bamberg Wendy , Janelle Sarah J , Jacob Jesse T , Bower Chris , Wilson Lucy , Vaeth Elisabeth , Lynfield Ruth , Vagnone Paula Snippes , Phipps Erin C , Hancock Emily B , Dumyati Ghinwa , Concannon Cathleen , Beldavs Zintars G , Cassidy P Maureen , Kainer Marion , Muleta Daniel , See Isaac
Published: October 2017

Background

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat in the United States because of high morbidity and mortality, few treatment options, and potential for rapid spread among patients. To assess for changes in CRE epidemiology and risk among populations, we analyzed CDC Emerging Infections Program (EIP) 2012–2015 surveillance data for CRE.

Methods

Active, population-based CRE surveillance was initiated in January 2012 at 3 EIP sites (GA, MN, OR) and expanded to 5 additional sites (CO, MD, NM, New York, TN) by 2014. An incident case was the first Escherichia coli, Enterobacter, or Klebsiella isolate (non-susceptible to at least one carbapenem and resistant to all third-generation cephalosporins tested) collected from urine or a normally sterile body site from a patient during a 30-day period. Data were collected from patients’ medical records. Cases were hospital-onset (HO) or long-term care facility (LTCF) onset if patients were in the respective facility ≥3 days prior to culture or at the time of culture; and community-onset (CO) otherwise. We calculated incidence rates based on census data for EIP sites and described by type of infection onset.

Results

A total of 1,582 incident CRE cases were reported in 2012–2015. Most cases (88%) were identified through urine cultures; 946 (60%) were female, and median age was 66 years (interquartile range: 55–77). The median incidence by site was 2.95 per 100,000 population (range: 0.35–8.98). Among the three sites with four full years of data, a different trend was seen in each (Figure). Trends in GA and MN were statistically significant, and no significant trend was seen in OR. Overall, 480 cases (30%) were HO, 524 (33%) were LTCF onset, and 578 (37%) were CO. Of CO cases, 308 (53%) had been hospitalized, admitted to a long- term acute care hospital or were a LTCF resident in the prior year.

Conclusion

CRE incidence varied more than 20-fold across surveillance sites, with evidence of continued increases in MN. Measuring impact of programs aimed at reducing CRE transmission in other regions will require obtaining local data to identify cases occurring during and after healthcare facility discharge. Further study of changes in incidence in some settings and areas might offer opportunities to refine and expand effective control strategies.

Disclosures

All authors: No reported disclosures.
Uropathogens and Antibiotic Resistance Among Nursing Home Residents - National Healthcare Safety Network (NHSN)
Authors: Eure Taniece , Stone Nimalie D , Thompson Nicola D , Bell Jeneita , Mungai Elisabeth
Published: October 2017

Background

Knowledge of urinary tract infection (UTI) pathogen and susceptibility patterns is necessary to inform antibiotic prescribing and monitor resistance. We describe bacterial pathogens and UTI antibiotic resistance patterns among residents in nursing homes (NHs) reporting to the National Healthcare Safety Network (NHSN) long-term care facility (LTCF) component.

Methods

All UTI events from January 1, 2013 to December 31, 2016 were included; up to three organisms per UTI event may be reported. Pathogen susceptibility results for selected antibiotics are reported as: Susceptible (S), Intermediate (I), Resistant (R), or Not tested (N). For this analysis, resistance was defined as I or R. We described pathogens and summarized antibiotic resistance only when ≥100 isolates of a bacterial species had susceptibility test results for a particular antibiotic reported to NHSN.

Results

In 166 NHs located in 37 states, a total of 4,054 pathogens were reported for 2,827 residents. Six organisms accounted for 81% of all UTI events (n = 3,599) (Table). A large proportion of Escherichia coli isolates, which accounted for 41% of uropathogens, were resistant to trimethoprim-sulfamethoxazole (35%) and levofloxacin (50%). Among Proteus mirabilis isolates, 53% were resistant to levofloxacin (Figure). Methicillin resistance was 74% among Staphylococcus aureus, and vancomycin resistance among Enterococcus spp. was 18%.

Conclusion

This is the first summary of UTI pathogens and susceptibility data from U.S. nursing homes reporting to a national surveillance system. Resistance to antibiotics commonly used to treat UTIs was high. Tracking and preventing resistance for key pathogens is a CDC priority and NHSN reporting by NHs provides a crucial opportunity to track antibiotic resistance, highlighting the importance of enrolling more NHs into NHSN.

Disclosures

All authors: No reported disclosures.
Prevalence of and Factors Associated with Clostridium difficile Co-infection Among Patients with Candidemia, United States, 2014–2016
Authors: Tsay Sharon , Benedict Kaitlin , Beldavs Zintars G , Farley Monica M , Harrison Lee H , Schaffner William , Gerth Taryn , Chiller Tom , Vallabhaneni Snigdha
Published: October 2017

Background

Candidemia and Clostridium difficile infection (CDI) are two common healthcare-associated infections (HAIs) and share risk factors such as antibiotic use and prolonged hospitalization. CDI and CDI treatment disrupt gut microbial diversity, allowing Candida overgrowth and translocation to the bloodstream. We describe CDI co-infection among patients with candidemia.

Methods

Population-based surveillance for candidemia was conducted through CDC’s Emerging Infections Program during 2014–2016. A case of candidemia was defined as a blood culture positive for Candida species collected from a surveillance area resident. Demographic and medical information, including occurrence of CDI was collected. We defined co-infection as CDI within 90 days of candidemia and performed bivariable analysis to assess factors associated with co-infection.

Results

Among 2129 cases of candidemia, 190 (9%) had CDI co-infection; 116 (5%) had CDI in the 90 days before candidemia (median: 10 days) and 60 (3%) had CDI following candidemia (median: 8 days). The median age of those with CDI-candidemia co-infection was 61 years and 100 (53%) were male. Compared with candidemia alone, the odds of CDI-candidemia co-infection was significantly greater for patients of black race (OR 1.41, 95% CI 1.05–1.90), those with diabetes (OR 1.68, 1.24–2.27), pancreatitis (OR 1.91, 1.01–3.61), or solid organ transplant (OR 4.15, 2.09–8.22). Those with co-infection had higher odds of certain healthcare exposures: hemodialysis (OR 2.27, 1.57–3.28), hospital stay in the past 90 days (OR 1.9, 1.37–2.64), ICU admission in the past 14 days (OR 1.78, 1.20–2.66), and central venous catheter (CVC) at the time of candidemia (OR 1.71, 1.19–2.46). There were no significant differences in 30-day mortality or in type of Candida species, although C. parapsilosis was less common in the co-infection group (8% vs. 13%).

Conclusion

Nearly one in ten patients with candidemia also had CDI co-infection. Black race, certain underlying conditions, hemodialysis, previous hospitalization, ICU stay, and the presence of a CVC were associated with co-infection. Clinicians should be vigilant for coinfection of CDI and candidemia, particularly in situations with associated risk factors.

Disclosures

W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee
Outcomes of women with laboratory evidence of Zika infection in pregnancy
Authors: Gunaratne Naiomi , Bartlett Michelle , Crane Anise , Greissman Samantha , Kwal Jaclyn , Lardy Meghan , Picon Michelle , Starker Rebecca , Tse Colette , Rodriguez Patricia , Gonzalez Ivan , Curry Christine
Published: October 2017

Background

Zika virus (ZIKV) infection in pregnancy is a global health concern. With onset of local transmission, obstetricians in Miami-Dade County, FL, United States, are now in the unique position of providing care to both pregnant women with locally-transmitted and travel-associated ZIKV infections. This study provides data regarding the testing and pregnancy outcomes of women with laboratory evidence of ZIKV infection in pregnancy.

Methods

A retrospective chart review was conducted using laboratory records of ZIKV testing (PCR and IgM) completed from January through December 2016 at multiple tertiary care centers located in Miami-Dade County. Testing was based on CDC guidelines at time of testing, leading to heterogeneity in tests performed. Data was extracted from charts of women with positive ZIKV PCR in serum and/or urine or positive ZIKV IgM with confirmatory, pending, or insufficient PRNT results. Routine obstetrics parameters and the presence of fetal or neonatal abnormalities were recorded.

Results

Of the 2327 pregnant women screened for ZIKV, 88 (3.8%) screened positive with PCR and/or IgM in serum or urine. Of those women with positive ZIKV testing, 53 (60%) had no documented ZIKV symptoms and 40 (45%) had no known travel history outside of Miami-Dade County during their pregnancy. Sixty-six women had antenatal ultrasounds, 14 (21%) of which ever had a head circumference or biparetial diameter measurement less than the third percentile, but none showed evidence of intracranial calcifications. Fifty-four women with positive testing have delivered: 46 at term and 8 preterm. Fifty-four infants have been born to women with positive ZIKV testing; 2 infants (1.98%) had documented congenital abnormalities. One infant was born with clinically-defined microcephaly (1.9%) and intracranial calcifications and the other had only intracranial calcifications. Ninety-four positive IgM tests were sent to the CDC for confirmatory plaque reduction neutralization testing (PRNT). 49 PRNT tests returned positive (ZIKV titer ≥10), while 28 returned negative (ZIKV titer < 10), representing a false-positive rate of 30.4%.

Conclusion

As this epidemic persists, data from this unique cohort of pregnant women with both local and travel-associated ZIKV exposure contributes to the growing knowledge base regarding implications of ZIKV in pregnancy.

Disclosures

All authors: No reported disclosures.
Changes in invasive pneumococcal disease among adults living with HIV following introduction of 13-valent pneumococcal conjugate vaccine, 2008–2014
Authors: Kobayashi Miwako , Adih William , Li Jianmin , Gierke Ryan , Almendares Olivia M , Watt James , Alden Nisha , Petit Susan , Farley Monica , Harrison Lee , Lynfield Ruth , Baumbach Joan , Thomas Ann , Schaffner William , Pilishvili Tamara
Published: October 2017

Background

People living with HIV (PLHIV) are at increased risk of invasive pneumococcal disease (IPD). Introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010 reduced adult IPD burden (indirect effects). In 2012, PCV13 was recommended in series with 23-valent polysaccharide vaccine (PPSV23) for adults with immunocompromising conditions, including PLHIV. We evaluated changes in IPD incidence in adults ≥19 years old with and without HIV after PCV13 introduction for children in 2010 and for immunocompromised adults in 2012. PCV13 coverage for adults 19–64 years old with indications was 6% in 2014.

Methods

IPD cases, defined as pneumococcal isolation from sterile sites, were identified through CDC’s Active Bacterial Core surveillance, with counts projected nationally. HIV status was obtained from medical records. Isolates were serotyped by Quellung reaction or PCR and grouped into PCV13-types, PPV11-types (unique to PPSV23), or non-vaccine types. We estimated IPD incidence (cases per 100,000 people) using national case-based HIV surveillance (for PLHIV) or US Census data (for non-PLHIV) as denominators. We compared IPD incidence in 2011–12 and 2013–14 to the pre-PCV13 baseline (2008–09) by serotype groups.

Results

Overall IPD incidence at baseline was 354.0 for PLHIV and 15.5 for non-PLHIV. From baseline to 2013–14, IPD rates declined in both PLHIV (-36.3%; 95% CI: -38.8, -33.7%) and non-PLHIV (-27.3%; 95% CI: -28.2, -26.5%). The largest reductions were noted in PCV13-type IPD in both PLHIV (Figure 1) and non-PLHIV (Figure 2) for both periods (-46.8% for PLHIV and -45.9% for non-PLHIV in 2011–12; -60.3% for PLHIV and -65.8% for non-PLHIV in 2013–14). Overall IPD rates were 22.8 (95% CI: 22.2, 23.4) times as high in PLHIV compared with non-PLHIV at baseline, and 19.4 (95% CI: 18.8, 20.0) times as high in 2013–2014.

Conclusion

IPD rates declined significantly in both PLHIV and non-PLHIV during the study period due to reductions in PCV13-type IPD; however, IPD rates remained 20-fold in PLHIV compared with non-PLHIV. Similar magnitude reductions in PCV13-type IPD in both groups and low PCV13 coverage in immunocompromised adults suggest that most of the observed decline is due to PCV13 indirect effects from childhood immunization.

Disclosures

L. Harrison, GSK: Scientific Advisor, Consulting fee; W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee
Leveraging the ART Advantage: diabetes and hypertension along the HIV care cascade in rural South Africa
Authors: Manne-Goehler Jennifer , Siedner Mark , Geldsetzer Pascal , Harling Guy , Montana Livia , Rohr Julia , Gomez-Olive Xavier , Wade Alisha , Davies Justine , Barnighausen Till
Published: October 2017

Background

Participation in antiretroviral therapy (ART) programs has been associated with greater utilization of care for diabetes and hypertension in rural South Africa. However, there is limited data about whether this apparent “ART advantage” translates into improved chronic disease management indicators.

Methods

The Health and Aging in Africa: a Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) is a cohort of 5,059 adults >40 in Agincourt. The study collects data on demographics, healthcare utilization, height, weight, blood pressure (BP), and blood glucose. HIV infection, HIV-1 RNA viral load (VL) and ART drug levels are tested via dried blood spots. We defined hypertension (HTN) based on measured BP or self-report of diagnosis by a healthcare provider or use of antihypertensive medication and diabetes (DM) by measured glucose or self-report of diagnosis by a healthcare provider or the use of DM medications. Our primary predictor of interest was stage along the HIV care cascade (HIV-, HIV+ not on ART, ART with a detectable VL, and with a suppressed VL). We compared the proportion in each sub-group who were aware of and treated for their hypertension or diabetes diagnosis, and fit adjusted linear regression models to estimate differences in systolic BP and glucose among those with diagnosed HTN or DM.

Results

Rates of HTN and DM were higher in HIV- than those with a suppressed VL (HTN: 68.4% v. 46.4%, DM: 12.9% vs.. 8.8%, respectively). However, the suppressed VL group had higher crude rates of awareness of HTN diagnosis and treated HTN as compared with the HIV- group (Aware: 69.9% vs.. 65.2%, p = 0.118; Treated: 50.2% vs.. 46.4%, p = 0.002). There were no significant differences in awareness or treatment rates for DM. In adjusted linear regression models among those with diagnosed HTN or DM, having a suppressed VL was associated with lower mean systolic BP (-5.94mm Hg, 95% CI: -9.68 – -2.20) and lower mean glucose (-3.74 mmol/L, 95% CI: -5.95 – -0.58), compared with being HIV-. This effect was preserved in models restricted to overweight and obese participants.

Conclusion

The HIV care delivery platform in South Africa appears to offer a vehicle for healthcare delivery for other chronic conditions. Future studies are needed to assess causality of these relationships, and to determine optimal methods of integrating chronic disease with HIV management.

Disclosures

All authors: No reported disclosures.
Prevalence of Systemic Hypertension Among HIV-Infected and HIV-Uninfected Young Adults
Authors: Ryscavage Patrick , Still William , Nyemba Vimbai , Stafford Kristen
Published: October 2017

Background

Advances in HIV care and treatment have resulted in perinatally infected children aging into adulthood. These patients may be at higher risk of HIV-associated non-AIDS conditions, including systemic hypertension (HTN). This study examined the association between HIV infection and the prevalence of HTN among young adults receiving care in West Baltimore.

Methods

We conducted a cross-sectional study of young adults with perinatally-acquired (PA) HIV frequency matched on race and sex to a stratified random sample of young adults with non perinatally-acquired (NPA) HIV and HIV-uninfected young adults (UI). All subjects were aged 18–29 years of age as of September 1, 2014. The outcome of HTN was ascertained through chart review (two systolic blood pressure measurements > = 140 mmHg or diastolic > = 90 mmHg at least three months apart; and/or physician prescription for an antihypertensive mediation). Logistic regression was used to estimate adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI) for the association between HIV infection and HTN. All data were collected from clinics within the University of Maryland Medical System.

Results

Three hundred and twenty-four patients were included in the study, 108 per exposure group. The prevalence of HTN was 23% among PA patients, 10% among NPA patients, and 9% among UI patients. The median age was 24 (IQR 22 - 26), 95% were African American, and 42% were male. PA patients had the highest prevalence of chronic kidney disease (CKD) and dyslipidemia (19% and 13% respectively) compared with NPA (1% and 3%) and UI (0% and 5%). PA patients had 3 (95% CI 1.4 - 6.6) times the base odds (controlling for matching variables) of prevalent HTN compared with UI patients and NPA had 1.1 times the base odds (95% CI 0.5 - 2.7) compared with UI patients. After controlling for race, gender, family history of HTN, and CKD, the prevalence odds ratio for HTN was 2.7 (95% CI 1.06 - 7.0) times higher for PA compared with UI, and 1.3 (95% CI 0.5 - 3.4) times higher for NPA compared with UI.

Conclusion

Our findings suggest that the prevalence of HTN among young adults with PA HIV is significantly higher than sex and race matched UI patients of similar age. HIV providers should carefully monitor these patients for the development of HTN, particularly as they enter adulthood.

Disclosures

All authors: No reported disclosures.
Impact of an Antibiotic Stewardship Program in Long-term Care Facilities: A Nursing Home Network Experience
Authors: Romero Fabian Andres , Mathews Evette , Flores Ara , Seo Susan
Published: October 2017

Background

Antibiotic stewardship program (ASP) implementation is paramount across the healthcare spectrum. Nursing homes represent a challenge due to limited resources, complexity of medical conditions, and less controlled environments. National statistics on ASP for long-term care facilities (LTCF) are sparse.

Methods

A pilot ASP was launched in August 2016 at a 270-bed nursing home with a 50-bed chronic ventilator-dependent unit. The program entailed a bundle of interventions including leadership engagement, a tracking and reporting system for intravenous antibiotics, education for caregivers, Infectious Disease (ID) consultant availability, and implementation of nursing protocols. Data were collected from pharmacy and medical records between January 2016 and March 2017, establishing pre-intervention and post-intervention periods. Collected data included days of therapy (DOT), antibiotic costs, resident-days, hospital transfers, and Clostridium difficile infection (CDI) rates. Variables were adjusted to 1,000 resident-days (RD) and findings between periods were compared by Mann–Whitney U test.

Results

A total of 47,423 resident-days and 1,959 DOT were analyzed for this study. Antibiotic use decreased from 54.5 DOT/1000 RD pre-intervention to 27.6 DOT/1000 RD post-intervention (P = 0.017). Antibiotic costs were reduced from a monthly median of US $17,113 to US $7,073 but was not statistically significant (P = 0.39). Analysis stratified by individual antibiotic was done for the five most commonly used antibiotics and found statistically significant reduction in vancomycin use (14.4 vs. 6.5; P = 0.023). Reduction was also found for cefepime/ceftazidime (6.9 vs. 1.3; P = 0.07), ertapenem (6.8 vs. 3.6; P = 0.45), and piperacillin/tazobactam (1.8 vs. 0.6; P = 0.38). Meropenem use increased (1.3 vs. 3.2; P = 0.042). Hospital transfers slightly trended up (6.73 vs. 7.77; P = 0.065), and there was no change in CDI (1.1 s 0.94; P = 0.32).

Conclusion

A bundle of standardized interventions tailored for LTCF can achieve successful reduction of antibiotic utilization and costs. Subsequent studies are needed to further determine the impact on clinical outcomes such as transfers to hospitals and CDI in these settings.

Disclosures

All authors: No reported disclosures.
Silent Polio Transmission: A Spatial Analysis
Authors: Jarvis Christopher , Altamirano Jonathan , Sarnquist Clea , Garcia-Garcia Lourdes , Reyes Leticia Ferreyra , Montero-Campos Rogelio , Cruz-Hervert Luis Pablo , Holubar Marisa , Talib Aisha , Purington Natasha , Halpern Meira , Behl Rasika , Ferreira Elizabeth , Delgado Guadalupe , Quintero Sergio Canizales , Desai Manisha , Edmunds John , Maldonado Yvonne
Published: October 2017

Background

As wild poliovirus is eradicated and countries switch from Oral Polio Vaccine (OPV) to Inactivated Polio Vaccine (IPV) per WHO recommendations, preventing circulation of vaccine-derived poliovirus is a top priority. However, spatial dynamics of OPV transmission are not well understood. Understanding these trends will improve resource targeting in the event of OPV reintroduction in undervaccinated communities. Mexico provides a natural environment to study OPV as it provides IPV routinely and bi-annual OPV campaigns.

Methods

Children in three villages near Orizaba, Mexico were randomized to three levels (10%, 30%, 70%) to receive OPV. We measured distance to nearest OPV shedding, and the amount of shedding close to unvaccinated individuals. We used maps to show the proximity and amount of shedding. Distance and density of shedding was analyzed separately using mixed effects logistic regression with random effects for household and time, adjusted for age, gender, area, and running water.

Results

The median distance to nearest OPV shedding was 85 meters (IQR 46, 145). The median number of shedding individuals within 200m was 3 (2, 6). Shedding and between household transmission occurred rapidly with unvaccinated individuals shedding on day one of the study (Figure 1). There was little evidence (Odds Ratio [OR] 1.04 (95% Highest Posterior Density [HPD] 0.92, 1.16)) of an association between distance (per 100 m) from OPV shedding and odds of shedding. There was some suggestion that the number of OPV shedding within 200 m may have some effect on unvaccinated shedding with OR 0.93 (HPD 0.·84, 1·01) but not at 100 or 500m. Results were consistent across the three villages.

Conclusion

Household structure appears to have limited value in predicting transmission of poliovirus shedding. The use of OPV results in rapid but low levels of transmission throughout the community and this would usually go undetected. The only way to avoid this is to not use OPV or to have strong controls such as quarantine, or strict hygiene protocols. After withdrawal of OPV worldwide the decision to reintroduce due to an outbreak should not be taken lightly as it appears a small amount of OPV is needed to result in transmission.

Disclosures

All authors: No reported disclosures.
Murine Typhus: a Common Cause of Acute Febrile Illness with Potential for Serious Complications
Authors: Afzal Zeeshan , Kallumadanda Sunand , Wang Feng , Hemmige Vagish S , Musher Daniel
Published: October 2017

Background

Individual cases and outbreaks of murine typhus have been documented in South Texas. We report 90 cases from Hidalgo County, Texas, enumerating complications and comparing results in children and adults.

Methods

We reviewed records of 101 patients in three hospitals in Hidalgo County, Texas, who had positive typhus serology (IgG or IgM titer ≥1:128) during 3 years, 2014–2016 and were categorized as suspected, probable or confirmed murine typhus cases in accord with CDC definitions. We excluded 11 cases because a concurrent infection may have confounded our tabulation of manifestations or there was insufficient information to make a clinical diagnosis.

Results

The majority presented with typical typhus: fever, headache, myalgias and fatigue. Rash, thrombocytopenia and elevated hepatic transaminases were frequent (Table). Clinical complications in 25 cases (28%) caused a less typical syndrome, including bronchiolitis, pneumonia, pancreatitis, cholecystitis, mesenteric adenitis, myositis, rhabdomyolysis, meningitis and septic shock. Procalcitonin was >0.5 in 10 of 14 (71%) cases. Once the diagnosis was suspected, patients were treated with doxycycline with a rapid response in every case. Generally fever disappeared within 24–36 hours of the first dose.

Conclusion

Murine typhus is a common endemic infection in South Texas. Although most patients had a typical syndrome, the disease is multisystem, and complications appeared in 28% of cases. Procalcitonin was usually elevated. Rats and opossums are common reservoirs for Rickettsia typhi, and a search for cases of murine typhus may be warranted in other parts of the US as well, so that treatment with doxycycline can be begun promptly.

Disclosures

All authors: No reported disclosures.
Invasive Pneumococcal Disease in Massachusetts Children 6 Years Following Introduction of PCV13
Authors: Yildirim Inci , Little Brent , Pelton Stephen I
Published: October 2017

Background

A second generation 13-valent-pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the childhood immunization schedule in Massachusetts (MA) beginning in April,2010

Methods

Cases of invasive pneumococcal disease (IPD) in children <18 years of age were detected through an enhanced surveillance system in MA since 2001. All cases in children and Streptococcus pneumoniae (SP) isolates, when available, are submitted to Department of Public Health (MDPH) and parents/physicians are interviewed for confirmation of demographic and clinical data. All available isolates are confirmed as SP, serotyped by Quellung reaction

Results

Three-hundred-thirty-seven IPD cases have been identified in MA children between 4.January 4, 2010 and 03.31.2017(Figure). Thirty-five(10.4%) were in infants <6 months; 41(12.2%) in children between 6 and 12 months; 60 (17.8%) in toddlers 12 to 24 months; 100 (29.7%) in children between 2 and 5 years of age and 101 (29.9%) were in children >5 years old. Among children under 2; incidence of IPD declined to 6.8/105 children (95% CI 2.6–11.1) in 2015/16 period which represents a 72.1% decline compared with 2010/11; however in 2016/17 IPD incidence increased by 41.2% to 9.6/105 (95% CI 4.6–14.6) for the first time since the implementation of PCV13.Bacteremia was the most common clinical presentation (62.9%) followed by pneumonia(30.5%) and CNS disease(6.6%). Children with at least one comorbidity were an increasing proportion of cases reaching 37.9% in 2016 (p 0.004). The overall mortality rate was 4.3%. Isolates from 301 (90.1%) were available for serotyping; vaccine serotypes (VST) were identified in 101 (33.6%) cases [serotype 19A(49 cases), 7F(21 cases), 3(18 cases), 19F (7cases), 6A(3 cases), serotypes 14, 18C and 5(1 case each)]. The proportion of VST disease declined to 24.1% from 59.2% over 6 years after PCV13 (p < 0.001). Serotypes 15BC (13.5%), 33F (12.5%) and 22F (12.5%) were the most common nonvaccine serotypes (NVST).

Conclusion

In the post-PCV13-era, IPD is primarily due to NVSTs and disproportionately observed in children with comorbid conditions. In the most recent year (4.1.2016 through 3.31.2017) an increase in incidence was observed in MA children after six years of declining cases following implementation of PCV13.

Disclosures

S. I. Pelton, Pfizer: Board Member and Grant Investigator, Consulting fee, Research grant and Speaker honorarium; Merck vaccines: Board Member, Consulting fee and Speaker honorarium; GSK: Board Member, Consulting fee and Speaker honorarium; Sequiris: Board Member, Consulting fee and Speaker honorarium
Trends in Neisseria Gonorrheae Antimicrobial Susceptibility in California, 2005–2016
Authors: Stoltey Juliet , Han Emily , Burghardt Nicole , Chow Joan , Bauer Heidi
Published: October 2017

Background

Resistant Neisseria gonorrheae (NG) is a growing concern in California, nationally, and globally. Since 1987, California has participated in the Gonococcal Isolate Surveillance Project (GISP), a Centers for Disease Control and Prevention-funded project to monitor trends in antimicrobial susceptibility in sentinel STD clinic sites throughout the United States. We sought to describe trends in California NG susceptibility to ceftriaxone (CRO) and azithromycin (AZI), recommended therapy for NG, for 2005–2016.

Methods

Per GISP protocol, cultures are collected from the first 25 men presenting with NG urethritis each month at GISP clinic sites in California, and antimicrobial susceptibility testing (AST) is performed via agar dilution at GISP regional laboratories. Reduced susceptibility (RS) to CRO was defined as minimum inhibitory concentration (MIC) ≥0.125 µg/ml and AZI MIC ≥2 µg/ml. Demographics and MIC trends over time were examined.

Results

Between 2005 and 2016, there were 9,692 NG isolates submitted in California GISP clinics. There were 24 (0.25%) isolates with RS to CRO and 92 (0.96%) isolates with RS to AZI. There was a higher proportion of isolates from men who have sex with men with RS to AZI (but not CRO) compared with men who have sex with women (chi-squared P-values: AZI = 0.0015; CRO = 0.70). In 2016, the percent of isolates demonstrating RS to AZI increased to 3.69% (n = 32), compared with 0.69% of isolates with RS to AZI in 2005–2015 (chi-squared P-value < .0001); there was no significant difference in the percent of isolates with RS to CRO in 2016 compared with prior years (Figure 1). Figures 2 and 3 demonstrate the distribution of AZI MICs and CRO MICs, respectively, from 2005–2016. There have been no isolates to date in California GISP with RS to both ceftriaxone and azithromycin.

Conclusion

Gonococcal surveillance data demonstrate an increase in the proportion of isolates with decreased susceptibility to azithromycin in 2016 in California compared with prior years. Although there has never been a documented treatment failure to the recommended therapy of CRO and AZI in California, clinicians should remain vigilant for treatment failures given these concerning increases.

Disclosures

All authors: No reported disclosures.
Gonorrhea (GC) and Chlamydia (CT) Infection in a Large, Well-Characterized Military Cohort: Prevalence, Incidence, Site of Infection, and Patient Characteristics
Authors: Eickhoff Christa , Wang Xun , Deiss Robert , Okulicz Jason , O’Bryan Thomas , Maves Ryan , Schofield Christina , Ferguson Tomas , Whitman Timothy J , Agan Brian , Ganesan Anuradha
Published: October 2017

Background

In the US military, routine extra-genital (EG) GC/CT testing in persons living with HIV was implemented in 2012. This study examines the prevalence/incidence and risk factors associated with genital (GU) and EG GC/CT infections in the US Military HIV Natural History Study (NHS), a cohort of HIV-infected Department of Defense beneficiaries.

Methods

Since 2012, willing NHS subjects have undergone nucleic acid-based tests (NAAT) to identify anorectal (AR)/ pharyngeal (PH) GC/CT infections. Incident cases had a positive test following an initial negative test. Risk factors for incident GC/CT infections were assessed with a multivariate Cox proportional hazards model.

Results

A total of 405 GC and 457 CT infections were observed among 1998 subjects (median age 28.7 years, 94% male, 44.1% African-American [AA]); 21% of GC and 18% of CT cases were re-infections. The incidence of AR GC, PH GC, and AR CT increased over time (P = 0.02, P = 0.03 and P = 0.02, respectively). Incident GC infections were associated with younger age [HR 0.61 per 5 year increase (0.57–0.66)], AA ethnicity [HR 1.46 (1.06–2.00)], higher viral load [HR 1.63 per log increase (1.47–1.80)] and a prior history of syphilis [HR 2.20 (1.62–2.99)]. Incident CT infections were associated with younger age [HR 0.7 per 5 year increase (0.66–0.74)], male gender [HR 5.82 (1.86–18.20)], higher viral load [HR 1.61 for each log increase (1.47–1.76)], lower CD4 count [HR 0.86 per 200 cell increase (0.79–0.95)], prior GC [HR 1.55 (1.15–2.08)] and prior syphilis [HR 2.16 (1.67–2.79)].

Conclusion

Incident AR GC and CT infections are increasing in the NHS and approximately 20% of infections were repeat infections. The increased incidence is attributable at-least in part to the increased uptake of EG testing. Our study highlights the importance of prevention in positive programs to reduce the risk of HIV transmission.

Disclosures

All authors: No reported disclosures.
Public Health Response to US Cases of Candida auris, a Globally Emerging, Multidrug-Resistant Yeast, 2013–2017
Authors: Tsay Sharon , Welsh Rory M , Adams Eleanor H , Chow Nancy A , Gade Lalitha , Berkow Elizabeth L , Lutterloh Emily , Quinn Monica , Chaturvedi Sudha , Fernandez Rafael , Giardina Rosalie , Greenko Jane , Southwick Karen , Kerins Janna L , Black Stephanie , Kemble Sarah K , Barrett Patricia M , Greeley Rebecca , Barton Kerri , Shannon Dj , Kallen Alexander , Shugart Alicia , Litvintseva Anastasia P , Lockhart Shawn , Chiller Tom , Jackson Brendan R , Vallabhaneni Snigdha
Published: October 2017

Background

Candida auris is an often multidrug-resistant yeast that causes invasive infections and, unlike most Candida species, spreads in healthcare facilities. CDC released a clinical alert in June 2016 requesting reporting of C. auris cases. We investigated cases to contain transmission and inform prevention measures for this novel organism.

Methods

Clinical cases were defined as C. auris from any clinical specimen from a patient in the United States. Response to cases included implementation of infection control measures, enhanced cleaning and disinfection, and testing of close contacts for C. auris colonisation (isolation from a person’s axilla or groin was defined as a screening case). Microbiology records were reviewed at reporting facilities for missed cases. All isolates were forwarded to CDC for confirmation, antifungal susceptibility testing, and whole-genome sequencing (WGS).

Results

As of April 13, 2017, 61 clinical cases of C. auris were reported from six states: New York (39), New Jersey (15), Illinois (4), Indiana (1), Maryland (1), and Massachusetts (1). All but two occurred since 2016 (Figure). An additional 32 screening cases were identified among contacts. Median age of clinical case-patients was 70 years (range 21–96); 56% were male. Nearly, all had underlying medical conditions and extensive exposure to healthcare facilities before infection. Most clinical isolates were from blood (38, 62%), followed by urine (8, 13%) and respiratory tract (5, 8%). Among the first 35 isolates, 30 (86%) were resistant to fluconazole, 15 (43%) to amphotericin B, and one (3%) to caspofungin. No isolate was resistant to all three. WGS revealed isolates from each state were highly related and different from other states, suggestive of transmission. Microbiology record reviews did not identify additional cases before 2016.

Conclusion

C. auris is an emerging pathogen, with similarities to multidrug-resistant bacteria, that has been transmitted in US healthcare settings. CDC and public health partners are committed to prompt and aggressive action through investigation of cases and heightened infection control practices to halt its spread.

Disclosures

All authors: No reported disclosures.
Time Trends in the Burden of Hospitalizations with Invasive Aspergillosis in the United States, 2004–2013
Authors: Zilberberg Marya D , Harrington Rachel , Spalding James , Shorr Andrew F
Published: October 2017

Background

Invasive aspergillosis (IA) remains a burdensome illness and is associated with substantial mortality. With increasing use of aggressive chemotherapy and immunomodulatory treatments, the prevalence of IA is likely to have grown. However, little is known about the current US burden of IA-related hospitalizations.

Methods

Using aggregated data available on the interactive website from the Agency of Healthcare Research and Quality’s Health Care Utilization Project Net, we examined the annual volume of IA-related hospitalizations in the United States, based on the presence of the ICD-9-CM codes 117.3, 117.9, and 484.6. Age-adjusted volumes were derived through population incidence calculated using year-specific censal and intercensal US population estimates available from the US Census Bureau. We additionally determined time trends in IA as the principal diagnosis (PD) and its associated charges.

Results

Between 2004 and 2013, the number of annual hospitalizations with IA grew from 29,774 (standard error, SE 2,425) to 51,870 (SE 2,642), a 74.2% overall increase. This increase was most notable among those aged 45–64 and 65–84 years. Regionally, the South contributed the plurality of the cases (40%), and the Northeast the fewest (17%) with the remainder split evenly between the West and the Midwest. When age-adjusting to year 2013, the growth in the volume of cases was slightly more modest (44.2%), going from 35,968 cases in 2004 to 51,870 in 2013. The proportion of IA hospitalizations in which IA was the PD dropped, from 14.4% in 2004 to 9.3% in 2013. Despite mean hospital length of stay (LOS) decreasing from 13.3 (SE 0.07) in 2004 to 11.5 (SE 0.6) days in 2013, the corresponding mean hospital charges rose from $71,164 (SE $5,248) to $123,005 (SE $9,738). The aggregate US inflation-adjusted hospital charges for IA PD rose from $436,074,445 in 2004 to $592,358,369 in 2013.

Conclusion

The rate of growth in IA-related hospitalizations in the United States between 2004 and 2013 was substantial. The plurality of cases appears to arise in the South. Despite a moderate decrease in LOS during the time period studied, there was a modest rise in the corresponding hospital charges. The aggregate US annual hospital bill for IA PD discharges is over $0.5 billion.

Disclosures

M. D. Zilberberg, Astellas Pharma Global Development, Inc.: grant investigator, research support R. Harrington, Astellas Pharma Global Development, Inc.: employee, former employee and salary J. Spalding, Astellas Pharma Global Development, Inc.: employee, salary A. F. Shorr, Astellas Pharma Global Development, Inc.: Consultant and Speaker’s Bureau, consulting fee, research support and speaker honorarium Cidara: consultant, consulting fee Merck: consultant, scientific advisor and Speaker’s Bureau, research support and speaker honorarium