bluuebunny/crossref_metadata_2025 huggingface dataset:
115. Results of a Targeted Neonatal Screening Program for Congenital Cytomegalovirus Infection in Montreal, Quebec
Authors: Renaud Christian , Smiljkovic Mina , Boucoiran Isabelle , Valois Silvie , Tapiero Bruce , Lamarre Valérie , Kakkar Fatima
Published: November 2018

Background

There remains considerable debate on the role of symptomatic, targeted vs. universal screening of newborns for congenital cytomegalovirus infection (cCMV). Here we report on a hospital-based targeted screening program for (1) infants who failed their newborn hearing screen and (2) infants of HIV-infected women, and compare this to the prevalence among infants tested for CMV following clinical suspicion of a congenital infection.

Methods

In November 2013, the “Programme québécois de dépistage de la surdité chez les nouveau-nés” (PQDSN), a provincially mandated hearing screening program, was implemented at Centre Hospitalier Universitaire Sainte-Justine, a tertiary maternal-child health center in Montreal, Quebec, along with CMV screening for all infants who failed their hearing test (excluding patients in the neonatal intensive care unit). Concurrently, beginning in April 2013, all infants of HIV-infected women were screened for cCMV infection within 48 hours of birth. The birth prevalence of cCMV infection in these targeted populations was compared with the prevalence among newborns tested for a clinical suspicion of cCMV.

Results

Out of 11 734 newborns screened for hearing through the PQDSN program between April 2014 and March 2018, 536 failed their initial hearing screen and 4 of these newborns tested positive for cCMV infection (0.75%). Out of a total of 130 HIV-exposed newborns born during this period, 116 were screened for cCMV and 3 (2.6%) confirmed positive. An additional 455 newborns were identified by the attending pediatrician as having a risk factor for any congenital infection; of these, 22 (5.3%) tested positive for cCMV. Using these combined methods, a total of 0.24% of newborns enrolled in the PQDSN program tested positive for cCMV infection.

Conclusion

The overall birth prevalence of cCMV was 0.75% among infants who failed their hearing screen, 2.6% among HIV exposed newborns, and 5.3% among infants with a clinical suspicion of a congenital infection. In the absence of a universal screening program for newborns, these results reinforce the importance of maintaining a high index of clinical suspicion for cCMV infection.

Disclosures

All authors: No reported disclosures.
116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition
Authors: Saccoccio Frances , Itell Hannah , Li Skukhang , Jenks Jennifer , Xie Guan , Pollara Justin , Gantt Soren , Permar Sallie
Published: November 2018

Background

Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. Development of an effective CMV vaccine is a public health priority. However, CMV vaccine development is limited by a poor understanding of the immune correlates of protection, including the role of CMV-specific IgG. Defining the role of passively acquired maternal IgG in the protection of half of the CMV-exposed, breastfeeding infants against postnatal CMV acquisition may inform CMV vaccine design

Methods

We analyzed CMV-specific humoral responses in 29 CMV-seropositive Ugandan mother–infant pairs. Seventeen mothers were HIV co-infected. Infants were followed weekly for postnatal CMV acquisition using saliva PCR. Twelve infants acquired CMV and 17 infants did not acquire CMV in the first 6 months of life. We compared CMV-specific IgG responses at delivery of mothers whose infants acquired CMV to mothers whose infants did not acquire CMV by 6 months of life and in the infants at 6 weeks of life. We also compared CMV-specific responses in mothers at delivery and infants at 6 weeks of life based on maternal HIV status.

Results

We found similar CMV-specific total IgG and IgG3 binding, avidity index, neutralization, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity responses in mothers whose infants did or did not acquire CMV by 6 months of life. Moreover, similar CMV-specific IgG binding and neutralization responses were also found between infants who did or did not acquire CMV by 6 months of life. Finally, CMV-specific IgG responses were similar in HIV-infected and uninfected mothers at delivery and in infants at 6 weeks of life regardless of perinatal HIV exposure.

Conclusion

CMV-binding and functional IgG responses do not appear to impact infant susceptibility to postnatal CMV acquisition in the first 6 months of life, and therefore other viral or immunologic factors contribute to the inefficiency of this mode of CMV transmission. Thus, to provide sterilizing protection against mucosal CMV acquisition, an antibody-based CMV vaccine would likely have to induce higher magnitude or qualitatively different responses than that of natural infection.

Disclosures

All authors: No reported disclosures.
118. Nasopharyngeal (NP) Bacterial Detection in Infants With Respiratory Syncytial Virus (RSV) Infection: Impact on Clinical Outcomes
Authors: Diaz Alejandro , Bunsow Eleonora , Garcia-Maurino Cristina , Naples Jeffrey , Juergensen Alexis , Mertz Sara , Wang Huanyu , Salamon Douglas , Leber Amy , Ramilo Octavio , Mejias Asuncion
Published: November 2018

Background

Previous studies suggest that RSV increases NP bacterial colonization and may facilitate infection. However, the role of NP colonization with potentially pathogenic bacteria (PPB) in the pathogenesis of RSV bronchiolitis is not well understood. We sought to determine the frequency, type, and density of NP PPB detection in infants with RSV infection compared with healthy controls (HC), and its association with clinical outcomes.

Methods

Single-center, prospective study of previously healthy infants with RSV infection and age-matched HC. Inpatients (IP) were enrolled within 24 hours of hospitalization, outpatients (OP) at the ED or primary clinics and HC at well-child visits. RSV infection and the following PPB: [S. pneumoniae, M. catarrhalis, H. influenzae, and S. aureus] were detected and quantified by PCR. We compared demographic, clinical characteristics, and outcomes of care according to NP PPB detection.

Results

From 2010 to 2018, we enrolled 815 infants: 664 with RSV infection [IP, 560; OP, 104] and 151 HC. RSV+ OP (6.1 [3.7–10.7] months) and HC (6.9 [3.8–10.8] months) were older than IP (2.5 [1.4–5.4] months; P < 0.001). Identification of ≥1 PPB was 89% in RSV+ infants [IP, 88%; OP, 90%] versus 63% of HC (P < 0.0001). While H. influenzae or >1 PPB detection was higher in RSV infection (P < 0.001), S. aureus detection predominated in HC (P < 0.05; Figure 1). Frequency of S. pneumoniae detection was comparable between groups; however, S. pneumoniae loads were one log higher in RSV+ infants versus HC (P = 0.001) adjusted for antibiotic use. Differences in colonization rates remained different in RSV+ infants versus HC across age ranges (<3, 3–6, >6–12, and >12–24 months; Figure 2). Last, RSV patients (both IP and OP) with S. pneumoniae or H. influenzae detection had fever more frequently (70%–74% vs. 25%–47%; P < 0.0001), higher clinical disease severity scores (P = 0.01), and higher blood neutrophil counts (34%–36% vs. 16%–19%; P < 0.001), versus those with M. catarrhalis, S. aureus detection or PCR negative. In addition, NP detection of H. influenzae in RSV children was associated with higher frequency of atelectasis/consolidation by chest X-ray (P < 0.005).

Conclusion

These data suggest that NP colonization with PPB is high in infants with RSV infection independent of age, and that specific bacteria, namely S. pneumoniae and H. influenzae, are associated with enhanced clinical disease severity.

Disclosures

A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support. O. Ramilo, Janssen Scientific Affairs, LLC: Consultant, Consulting fee. A. Mejias, Janssen: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Abbvie: CME talks, Speaker honorarium.
119. Prospective Validation of a 3-Gene Signature for Tuberculosis Diagnosis, Predicting Progression and Evaluating Treatment Response
Authors: Warsinske Hayley , Rao Aditya , Moreira Flora Martinez Figueira , Dos Santos Paulo Cesar Pereira , Liu Andrew , Scott Madeleine , Malherbe Stephanus , Ronacher Katharina , Walzl Gerhard , Winter Jill , Sweeney Timothy E , Croda Julio , Andrews Jason R , Khatri Purvesh
Published: November 2018

Background

The World Health Organization (WHO) has identified the need for a nonsputum-based triage test for tuberculosis (TB) that can be used to identify those who need further testing to identify active disease. We investigated whether our previously described 3-gene TB score could identify individuals with active tuberculosis (ATB) prior to seeking care (“active case detection”) and how the 3-gene TB score correlated with the timing of disease onset, disease severity, and response to treatment.

Methods

This study consisted of a prospective nested case–control trial, Brazil Active Screening Study (BASS; 2016), and re-analysis of data from 2 prospective cohort studies, the Adolescent Cohort Study (ACS; 2005–2007), and the Catalysis Treatment Response Cohort (CTRC; 2010–2013). The BASS case–control subcohort contained 81 adults (ages 20–72 years, 33 ATB, 48 controls). The ACS contained 153 adolescents (ages 12–18 years, 46 ATB, 107 LTBI). The CTRC-contained 138 adults (ages 17–67 years, 100 ATB, 17 other lung disease patients, 21 healthy controls).

Results

The 3-gene TB score diagnosed ATB patients with high accuracy: BASS cohort AUC = 0.87 (95% CI = 0.82–0.91, Figure 1A), ACS cohort AUC = 0.86 (95% CI = 0.76–0.97, Figure 1B), and CTRC AUC = 0.93 (95% CI = 0.88–0.97). In the ACS, the 3-gene TB score predicted progression from LTBI to ATB 6 months prior to positive sputum test (AUC = 0.86; 95% CI = 0.79–0.92, Figure 1B). In the CTRC, the 3-gene TB score correlated with glycolytic activity ratio of PET-CT at baseline (correlation = 0.54, P = 3.98 × 10−8, Figure 1C) and at the end of treatment (correlation = −0.408, P = 3.72 × 10−5). In the CTRC, the 3-gene TB score at baseline predicted the likelihood of prolonged sputum positivity following treatment initiation and treatment response at 6 months (P = 3.6 × 10−5). Collectively, across all cohorts, the 3-gene TB score identified ATB patients with 90% sensitivity and 70% specificity, and had 99% negative predictive value (NPV) at 5% prevalence.

Conclusion

Across 3 independent prospective cohorts, the 3-gene TB score closely approaches the WHO target product profile benchmarks for non-sputum–based triage test at high NPV. These performance characteristics make it a potential test for ruling out ATB and for monitoring disease status.

Disclosures

T. E. Sweeney, Inflammatix, Inc.: Employee and Shareholder, Salary. P. Khatri, Inflammatix Inc.: Board Member, Equity
127. Urinary Tract Infection Incidence Is Associated with Recent Environmental Temperatures
Authors: Simmering Jacob , Sewell Daniel , Polgreen Linnea , Polgreen Philip M
Published: November 2018

Background

Urinary tract infections (UTI) are one of the most common infections and the incidence of UTIs is seasonal, peaking in summer months. Relative to other times of the year, incidence of UTIs during the June to September period is approximately 10% greater. Prior work has suggested that a cause of this seasonality may be warmer temperatures during summer months. However, this work focused on inpatients and used average monthly temperatures.

Methods

We identified all UTI cases located in 1 of 397 metropolitan statistical areas (MSA) in the contiguous United States between 2011 and 2016 using the Truven Health MarketScan databases. A total of 192 million person-years of data were included in this dataset and a total of 21,975,244 outpatient claims for UTI were identified by ICD-9 (599.0) and ICD-10 (N39.0) codes. Weather data for each MSA and date were obtained from the National Centers for Environmental Information. We computed the mean temperature during the period 3 to 8 days prior to the service date of the claim. A Poisson generalized linear model was used to estimate the effect of temperature on the count of UTI cases adjusted for MSA size, day-of-week, and week-of-year.

Results

The effect of temperature on UTI risk was significant (likelihood ratio test P < 0.0001). Relative to times when the average temperature 3–8 days prior was 40.1–45°F, UTI incidence exhibited a dose–response relationship as shown in the figure.

Conclusion

Incidence of UTIs exhibits a dose–response pattern with temperature during the period 3–8 days prior to presentation. This pattern persists after adjustment for seasonal factors. These results suggest a causal relationship between warm weather, and UTI risk may exist and warrants further investigation.

Disclosures

All authors: No reported disclosures.
128. Sexually Transmitted Infections Among Adolescent Girls in Thika, Kenya
Authors: Yuh Tiffany , Kiptinness Catherine , Selke Stacy , Oluoch Lynda , Magaret Amalia , Ngure Kenneth , Wald Anna , Mugo Nelly , Roxby Alison C
Published: November 2018

Background

Globally, the rates of sexually transmitted infections (STIs) are highest among 15- to 24-year-old girls, especially in Sub-Saharan African countries where the adolescent sexual health is poor. Recruiting girls presexual debut could identify risk factors for STI acquisition.

Methods

We recruited a prospective cohort of “low-risk” adolescent girls aged 16–20 in Kenya. To be eligible, girls were HIV and HSV-2 seronegative and reported no history of sexual intercourse or reported having sex with only one partner. Demographic data were collected, and girls had nucleic acid testing of vaginal swabs for Neisseria gonorrhea, Chlamydia trachomatis, and Trichomonas vaginalis, and vaginal gram stains for bacterial vaginosis (BV).

Results

We enrolled 400 girls, with a median age of 18.6 years. In this cohort, 322 (80.5%) girls reported never having had sex, while 78 (19.5%) reported prior sex with 1 partner. Of those reporting prior sex, only 20 (25.6%) reported contraception use in the last 3 months, with 60% using only emergency contraceptive pills. The median age of sexual partners was 22 (IQR 19–25). Of the 373 participants with an STI swab result, 49 participants (13.1%) tested positive for STIs at entry into the study, with 41 chlamydia, 5 gonorrhea, and 3 trichomonas cases. Of these 49 participants, 33 (67.3%) had denied prior sexual intercourse. Testing positive for STIs was, however, significantly different among those reporting prior sexual intercourse vs. reporting never having had sex, 21.1% vs. 11.1% (P = 0.02). BV was rare (5.6%) in the cohort, with 90% of participants with a normal Nugent score of 0–3.

Conclusion

In the initial testing of a sexually inexperienced cohort of girls, we found unexpectedly high numbers of prevalent STIs, especially chlamydia which is not routinely screened for in Kenyan settings. Additionally, lack of sexual activity appeared overreported. BV was rare, with much lower prevalence than in adult women in Africa. Our data suggest that prior to initiation of sexual activity, most girls in this Kenyan cohort have vaginal microflora that is dominated by Lactobacillus. Interventions to address STIs, including pre-exposure prophylaxis for HIV, should be targeted at girls at a young age, presexual debut, and in nonmedical settings where girls can be reached who do not selfidentify as at risk for STI.

Disclosures

All authors: No reported disclosures.
158. The Effect of Insurance Coverage on Appropriate Selection of Hospital Discharge Antibiotics for Staphylococcus aureus Bacteremia
Authors: McHale Thomas , Medder Jim , Lyden Elizabeth , Geske Jenenne , Rupp Mark E , Van Schooneveld Trevor
Published: November 2018

Background

Inappropriate or inadequate antimicrobial therapy of Staphylococcus aureus bacteremia (SAB) is associated with worsened outcomes. The impact of insurance coverage on appropriate selection of antibiotics is poorly understood. In patients diagnosed with SAB, we assessed the impact of insurance coverage on appropriate selection and duration of antibiotics at discharge.

Methods

We analyzed 273 patients who were diagnosed with SAB during their hospitalization at Nebraska Medicine and were discharged on antibiotics in 2015 and 2016. Antimicrobial therapy was deemed inappropriate if (i) total treatment duration was less than 14 days, (ii) oral delivery route was used, (iii) vancomycin was used to treat methicillin sensitive S. aureus in non-β-lactam allergic patients, or (iv) any penicillin or cephalosporin was used to treat methicillin-resistant S. aureus. Insurance was categorized broadly into (i) no insurance, (ii) Medicaid, (iii) Medicare, and (iv) Commercial. We collected data on a suite of additional variables that included: type of infectious disease (ID) inpatient consult and location of discharge. Logistic regression was used to determine the odds of being prescribed inappropriate therapy in univariate and multivariate analyses and likelihood ratio tests (LRT) were used to evaluate the strength of evidence.

Results

In unadjusted models, not having insurance was associated with inappropriate antimicrobial therapy (Reference Group: Any insurance; OR No insurance 4.71; LRT P = 0.027). Two additional risk factors for inappropriate therapy were identified in unadjusted models: discharge location (Refrence Group: Nursing assistance; OR Home without assistance 3.37; 95% CI 1.34–8.46; LRT P = 0.008) and lack of an ID consult (Reference Group: Academic team; OR Not consulted 26.8, 95% CI 7.66–93.8; LRT P < 0.001).

Conclusion

We found strong evidence that not having insurance, being discharged to home without assistance, and not having an inpatient ID consult are risk factors for being prescribed inappropriate antimicrobial therapy for SAB upon hospital discharge; however, the sparsity of outcomes prevents us from drawing causal inferences. This study adds to the extensive body of evidence that has shown that uninsured patients tend to have suboptimal therapeutic choices.

Disclosures

All authors: No reported disclosures.
160. Reduction in the Spread of Hospital-Associated Infections Among Pediatric Oncology Patients in an Animal-Assisted Intervention Program from a Canine Decolonization Procedure
Authors: Dalton Kathryn , Ruble Kathy , DeLone Alexandra , Frankenfield Pam , Walker Destiny , Ludwig Shanna , Ross Tracy L , Jaskulski Janice , Carroll Karen C , Rankin Shelley , Morris Daniel , Chen Allen , Davis Meghan
Published: November 2018

Background

Animal-assisted interventions (AAI), the use of animals as a complementary therapy in holistic patient care, has shown many positive outcomes. However, therapy animals can serve as mechanical vectors of hospital-associated infections (HAI), e.g., methicillin-resistant Staphylococcus aureus (MRSA). This pilot study assessed for transmission of HAIs among therapy animals, patients, and the hospital environment. We tested the effectiveness of a novel decolonization protocol for therapy dogs to reduce the risk of transmission of HAIs and enhance AAI program sustainability. Our hypothesis was that HAI transmission occurs from positive child to child, with the dog as an intermediary fomite.

Methods

Before and after child–animal interaction, we sampled patients, dogs, and the environment, and collected vital statistics and survey data from patients. MRSA was detected in samples by culture and molecular testing. Therapy dog handlers performed normal pre-visit practices for 2 control visits, then switched to a decolonization protocol (chlorhexidine-based shampoo prior to the visit, and chlorhexidine wipes on the fur during the visit) for 2 intervention visits.

Results

We evaluated 45 children and 4 therapy dogs over 13 visits. Children had decreased blood pressure and heart rate, and reported improved mental health scores post visit. MRSA conversion was identified from 10.2% of the children and 38.5% of the dogs, while 93% of the environmental samples were MRSA positive both pre and post. Patients that interacted closely with the dog had 8.01 times higher odds (95% CI 1.1–15.2) of MRSA conversion compared with patients who barely interacted with the dog. When stratified by intervention group, the MRSA conversation odds ratio of close interaction was 0.93 (95% CI 0.1–10.8) when the dog was decolonized versus 9.72 (0.9–99) when not decolonized.

Conclusion

This study showed the potential for AAI visits to improve physiological and mental health of pediatric outpatients. A risk of HAI exposure to patients from interaction with the dog was found, but this effect was nullified by the decolonization procedure. Future research is needed to increase the safety of this valuable alternative therapy.

Disclosures

All authors: No reported disclosures.
165. Mycobacterium tuberculosis Produces Molecules That Trigger Nociceptive Neurons to Activate Cough
Authors: Ruhl Cody , Kindt Lexy , Khan Haaris , Stamm Chelsea E , Pasko Breanna , Franco Luis , Shiloh Michael U
Published: November 2018

Background

A hallmark symptom of active pulmonary tuberculosis vital for disease transmission is cough. The current paradigm for tuberculosis-related cough is that it results from airway damage or irritation. However, there is limited experimental data to support this theory, and whether Mycobacterium tuberculosis (Mtb) induces cough to facilitate its own transmission has not been explored. The cough reflex is a complex and coordinated event involving both the nervous and musculoskeletal systems initiated by particulate or chemical molecules activating nociceptive neurons, which sense pain or irritation. This activation induces a signaling cascade ultimately resulting in a cough. Respiratory nociceptive neurons innervate the airway of humans and most mammals, and thus are poised to respond to noxious molecules to help protect the lung from damage. Because Mtb is a lung pathogen, cough is a primary mechanism of Mtb transmission, and respiratory nociceptive neurons activate cough, we hypothesized that Mtb produces molecules that stimulate cough, thereby facilitating its spread from infected to uninfected individuals.

Methods

We used an in vitro neuronal activation bioassay to fractionate, identify, and characterize Mtb cough-inducing molecules. We also measured cough in vivo in response to pure Mtb-derived cough molecules and during Mtb infection using a guinea pig model.

Results

We found that an acellular organic extract of Mtb triggers and activates nociceptive neurons in vitro with a neuronal response that is as robust as the response to capsaicin, an established nociceptive and cough-inducing molecule. Using analytical chemistry and our neuronal bioassay, we then isolated 2 molecules produced by Mtb that activate nociceptive neurons. Both the organic Mtb extract and purified molecules alone were sufficient to induce cough in a conscious guinea pig cough model. Finally guinea pigs infected with wild-type Mtb cough much more frequently than guinea pigs infected with Mtb strains unable to produce nociceptive molecules.

Conclusion

We conclude that Mtb produces molecules that activate nociceptive neurons and induce cough. These findings have significant implications for our understanding of Mtb transmission.

Disclosures

All authors: No reported disclosures.
855. Impact of FDA Black Box Warning on Fluoroquinolone and Alternative Antibiotic Use in Southeastern US Hospitals
Authors: Yarrington Michael , Anderson Deverick J , Ashley Elizabeth Dodds , Jones Travis , Johnson Melissa , Lokhnygina Yuliya , Sexton Daniel , Moehring Rebekah W
Published: November 2018

Background

Many antimicrobial stewardship programs have set goals to reduce the use of fluoroquinolones because of risks of causing C. difficile and other adverse safety events. The US Food and Drug Administration issued a black box label warning for fluoroquinolones in June 2016 recommending avoidance of this class for treatment of uncomplicated infections.

Methods

We performed a retrospective cohort study of antimicrobial use (AU) data in 29 southeastern United States hospitals from 2013 to 2017. An interrupted time series approach with segmented negative binomial regression modeling was used to estimate the longitudinal trend and effect of the FDA safety announcement on AU rates. Fluoroquinolone and alternative antibiotic agent use rates were measured as days of therapy (DOT) per 1,000 patient days. Alternative antibiotics were analyzed individually or in groups (e.g., community-onset agent group included ceftriaxone, cefotaxime, and ertapenem).

Results

Hospital AU data for the 60-month period included a total of 6,685,950 patient days; 8 to 29 hospitals contributed AU data to estimates each month. FQ use rates declined at a consistent rate of approximately 1 DOT/1,000 patient days per month resulting in an overall 10% decrease prior to the FDA warning. A significant drop in FQ use rates occurred at the time of the announcement (P = 0.002), but there was no significant change in trend [rate ratio (RR) 0.89, 95% CI 0.79–1.01, P = 0.07, Figure 1]. Alternative antibiotic use significantly increased for the following antibiotic groups after the warning: community-onset agents (RR 1.24, 95% CI 1.11–1.38), atypical agents (RR 1.40, 95% CI 1.19–1.66), and third-generation cephalosporins (RR 1.54, 95% CI 1.19–1.65). Antipseudomonal β-lactam use remained stable (RR 0.96, 95% CI 0.88–1.05, P = 0.3).

Conclusion

Fluoroquinolone use was declining in our network prior to the FDA announcement and continued to decline after 2016. This is likely due to stewardship activities focusing on quinolone-sparing treatment guidelines. AU shifted away from FQ toward third-generation cephalosporins and atypical agents.

Disclosures

All authors: No reported disclosures.
856. Impact of Early Discontinuation of Antimicrobial Therapy on Survival in Culture-Negative Clinically Suspected Serious Infection: An Electronic Health Record-Based Analysis From 111 US Hospitals
Authors: Kadri Sameer S , Klein Eili , Gandra Sumanth , Rhee Chanu , Klompas Michael , Laxminarayan Ramanan
Published: November 2018

Background

Up to 40% of inpatients started on antibiotics for suspected infection have negative cultures from all tested body sites. The optimal duration of treatment for these patients is unknown.

Methods

Adults admitted to 111 hospitals between 2009 and 2015 with clinically suspected serious infection but negative cultures were identified. We deemed patients to have clinically suspected serious infection if blood cultures were drawn on hospital day 1 or 2 and IV or PO antibiotics were initiated on the day of or after blood culture draw and continued for ≥3 days. We compared outcomes for patients treated with 3–4 vs. ≥5 days of antibiotics. We excluded patients on vasopressors beyond day 2. We calculated odds ratios for in-hospital mortality (including discharge to hospice), C. difficile infection (CDI), subsequent sepsis, and antibiotic restarts >1 day after discontinuation using logistic regression, adjusting for age, race, Sequential Organ Failure Assessment (SOFA) score, and several co-morbidities; findings were confirmed by determining the average treatment effect on the treated (ATET) using propensity matching.

Results

We identified 179,421 patients with clinically suspected serious infection. Of these, 71,786 (40%) had all negative cultures; 26,437 (37%) were treated with 3–4 days of antibiotics; and 45,349 (63%) were treated with ≥5 days. Patients treated with shorter courses were younger, had lower SOFA scores, and were less likely to have concomitant sepsis. There was no difference in mortality for short vs. long course treatment (4.7% vs. 6.5%, aOR 1.01 [95% CI 0.93–1.11]; ATET=1.002 [0.998–1.006]; P = 0.46). Patients treated with short courses were less likely to develop CDI (aOR 0.55 [0.47–0.66]) or subsequent sepsis (aOR 0.26, 0.17–0.41) but more likely to have antibiotic restarts (3.9% vs. 3.6% aOR 1.53 [1.35–1.73]). Mortality was lower, however, amongst patients with antibiotic restarts who initially received short (vs. long) courses (aOR 0.76 [0.57–1.00]).

Conclusion

We found no difference in mortality for patients with culture-negative clinically suspected serious infection treated with 3–4 days vs. ≥5 days. Patients treated with short courses had less CDI and sepsis after discontinuation of antibiotics but higher rates of antibiotic restarts. A randomized, controlled trial is warranted to confirm or refute these findings.

Disclosures

R. Laxminarayan, Merck: Board Member, Educational grant.
864. Therapeutic Immunosupression to Treat Rabies Encephalitis
Authors: S Divyashree , Shrivastava Archana , Sontakke Tushar , Venkitachalam Anil
Published: November 2018

Background

Rabies is nearly universally fatal with about 60,000 annual deaths globally; <0.1% cases survive. Reports of therapeutic coma leading to survival are outnumbered by reports of failure. On the basis of personal discussions with a leading rabies expert (Dr Rodney Willoughby), we hypothesized that limiting CNS immune response based on CSF antibody titre (ABT) might prove useful. We report on successful use of immunosuppression in 1 patient.

Methods

A 26-year-old male was admitted with 2-day history of flu-like syndrome. He had category III dog bite on face 17 days prior. RIG was not given due to nonavailability; he had received ARV day 0, 3, 7, and 14 on time. On 4th day of admission (day 0), neurological features started—difficulty in walking and diplopia; hydrophobia was noted. Working diagnosis of rabies was made. MRI brain on day 1 showed subtle abnormal T2 and flair hyper intensities in pons, medulla, and left hippocampus. CSF (day 1) showed 105 cells; all lymphocytes. The RFFIT serum and CSF ABTs and rabies PCRs are tabulated below. Since ADEM was a possibility, he was begun on IVIg. Work up for other viral encephalitis was negative. Repeat CSF ABT on day 6 confirmed rabies. Postulating risk of death due to cerebral edema due to CNS immune response, dexamethasone (dexa) 6 mg/kg/day in 4 divided doses was begun on day 8. Serial MRI and CSF were done. Dexa taper was done based on MRI and CSF ABT. Intensive supportive care was given.

Results

MRI on day 9 and day 12 showed no cerebral edema. Dexa taper was started from day 13 by half every alternate day; it was given till day 28. By day 17, there was intermittent eye opening, withdrawal to pain and some orofacial and limb movements. Further recovery had waxing and waning course. Now he is nearly 1 year post rabies encephalitis. He is unable to talk or comprehend, but can sit independently and is able to walk with support.

Conclusion

Immunosuppressive therapy with dexa to improve outcomes in rabies seems an exciting option. Optimal dose, time of start, and taper schedule need further studies. CSF ABT-based tapering appears promising. Larger studies with this approach are needed.

Disclosures

All authors: No reported disclosures.
867. Upregulated Matrix Metalloproteinase-2 Relates to Milder Hearing Impairment in Bacterial Meningitis
Authors: Savonius Okko , Roine Irmeli , Alassiri Saeed , Tervahartiala Taina , Helve Otto , Fernandez Josefina , Peltola Heikki , Sorsa Timo , Pelkonen Tuula
Published: November 2018

Background

Hearing impairment is a well-recognized sequela caused by bacterial meningitis, but the underlying pathophysiology remains largely unknown. Matrix metalloproteinase-2 (MMP-2) is known to affect neuronal cell damage and survival in different diseases of the brain. We investigated whether levels of MMP-2 in the cerebrospinal fluid (CSF) relate to the extent of hearing impairment in children with bacterial meningitis.

Methods

Clinical data of 179 children were obtained from a previous clinical trial examining the adjuvant treatment of bacterial meningitis in Latin America in 1996–2003. At discharge or shortly thereafter, the ability to hear was measured with brain stem evoked response audiometry or traditional pure tone audiometry. Levels of CSF MMP-2 on admission (CSF1, n = 161) and 12–24 hours later (CSF2, n = 133) were assessed by zymography. The combined results for the detected pro-form and active MMP-2 were compared with the audiological outcome of the patients.

Results

MMP-2 was detected in half of both the CSF1 and CSF2 samples. The median densitometric values with interquartile ranges (IQRs) were 0.04 (IQR 0.00–0.29) for CSF1 and 0.00 (IQR 0.00–0.33) for CSF2. Detectable MMP-2 associated with milder hearing impairment in CSF1 (P = 0.05), but not in CSF2 (P = 0.1). Patients who were deaf at discharge had lower levels of MMP-2 in both samples (CSF1, P = 0.05; CSF2, P = 0.04), compared with patients who were not deaf. A MMP-2 level over the 75th percentile in CSF1 predicted lower odds of any audiological sequelae (odds ratio 0.30, 95% confidence interval 0.14–0.68, P = 0.004).

Conclusion

The upregulation of MMP-2 in the CSF associated with a better audiological outcome in children with bacterial meningitis. The results suggest that MMP-2 might play a protective role in the development of hearing sequelae due to bacterial meningitis.

Disclosures

All authors: No reported disclosures.
869. Evaluation of Broad-Spectrum Antibiotic De-Escalation in Patients with Health-Care Associated Pneumonia (HCAP) and No Microbiological Diagnosis
Authors: Patel Twisha S , Petty Lindsay , Conlon Anna , Eschenauer Gregory , Nielsen Daniel , Vaughn Valerie , Kaye Keith S , Malani Anurag , Osterholzer Danielle , Thyagarajan Rama , Flanders Scott , Gandhi Tejal N
Published: November 2018

Background

Broad-spectrum (BS) antibiotics directed against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) are commonly used for health-care associated pneumonia (HCAP) treatment. Many patients with HCAP do not have a microbiologically confirmed diagnosis. The goal of this study was to evaluate the impact of antibiotic de-escalation on clinical outcomes in patients with HCAP without a microbiological diagnosis.

Methods

This is a retrospective cohort study of adult, non-ICU, medical patients hospitalized with HCAP between January 2016 and February 2018 at 46 Michigan hospitals. Exclusions included extrapulmonary infection, severe immune suppression, or clinical instability on day 4. Included patients: (1) lacked any positive culture (blood/sputum); (2) started on empiric anti-P. aeruginosa and anti-MRSA therapy by hospital day 2; (3) switched to a narrow-spectrum (NS) regimen (no anti-P. aeruginosa or anti-MRSA coverage) or maintained on BS antibiotics (anti-P. aeruginosa ± anti-MRSA) by therapy day 4 (Figure 1). Mortality, readmission, Clostridium difficile infection, and adverse events from antibiotics were compared between the BS and NS groups. Data were analyzed using logistic generalized estimating equation models and inverse probability of treatment weighting.

Results

Of 363 patients with HCAP included, 73 (20%) were switched to an NS regimen. Of 290 patients maintained on anti-PSA BS regimens, 47.6% also continued anti-MRSA therapy. The median age was 72 (IQR, 61–81) and Charlson comorbidity index was 4 (IQR, 2–6) of the entire cohort. Baseline characteristics were similar between BS and NS groups, except more patients had chronic kidney disease in the BS group. On multivariable analysis, no other baseline factors were found to be associated with use of BS antibiotics on day 4. Both total and IV antibiotic duration were longer in the BS group (10 vs. 8 days, P = 0.002, and 4 vs. 3 days, P < 0.001, respectively). On adjusted analysis, there were no differences in patient outcomes (Figure 2).

Conclusion

Among patients with HCAP started on empiric MRSA and PSA coverage without microbiological diagnosis, clinical outcomes were similar in patients switched to an NS antibiotic and those maintained on BS antibiotics. Our findings suggest a potential role for antimicrobial stewardship in promoting antibiotic de-escalation in this population.

Disclosures

All authors: No reported disclosures.
875. Sex Differences in Academic Achievement and Faculty Rank in Academic Infectious Diseases
Authors: Manne-Goehler Jennifer , Kapoor Neena , Blumenthal Daniel , Stead Wendy
Published: November 2018

Background

Sex differences in faculty achievement in academic medicine have been described, but little is known about these differences in infectious diseases (ID). This study assesses differences in faculty rank between female and male infectious disease faculty with academic appointments at US medical schools.

Methods

We analyzed a complete database of US physicians with medical school faculty appointments in 2014. This database consists of a linkage between the American Association of Medical Colleges faculty roster and a comprehensive physician database from Doximity, a professional networking website for doctors and includes physician age, sex, years since residency completion, publications, National Institutes of Health grants, and registered clinical trials for all academic physicians by specialty. We estimated sex differences in key metrics of academic achievement, including publications and faculty rank, among faculty physicians within ID. Multivariable regression models with medical school-specific fixed effects were used to assess sex differences in full professorship by specialty and the relationship between these factors and achieving the rank of full professor within ID.

Results

Among 2,016 academic ID physicians [Female: 742 (37%)], women accounted for 48.1% of assistant professors, 39.7% of associate professors, and 19.2% of full professors, when compared with men at each level. Women faculty members were younger than men (mean: 48.4 years vs. 54.0 years, P < 0.001) and had fewer total (mean: 24.1 vs. 37.8, P < 0.001) and first/last author publications (mean: 16.7 vs. 32.2, P < 0.001). In adjusted models, the rate of full professorship (vs. assistant or associate) among female compared with male infectious disease physicians was large and highly significant (absolute adjusted difference = −8.0%; 95% confidence interval [CI]: −11.9% to −4.1%). This adjusted difference was greater in ID than in cardiology (−4.7%, 95% CI: −7.9% to −1.3%), hematology (−1.5%, 95% CI: −6.2% to 3.2%), or endocrinology (−0.2%, 95% CI: −4.9% to 4.6%).

Conclusion

Significant sex differences in publications and achieving the rank of full professor exist in academic ID, after adjustment for multiple factors known to influence these outcomes. Greater efforts should be made to address equity in academic ID.

Disclosures

All authors: No reported disclosures.
920. A Sharp Fall in Antibiotic Use in Infants Is Correlated With a Population-Wide Reduction in Asthma Incidence for Children Under 5
Authors: Patrick David , Mamun Abdullah , Rasali Drona , Rose Caren , Marra Fawziah
Published: November 2018

Background

Antibiotic use in infants <1 is associated with increased relative risk (~1.5) for childhood asthma in cohort studies. This may be mediated by removal from the infant microbiome of organisms shown to protect against asthma, a hypothesis supported by experiment. We launched this study to see whether reductions in antibiotic use at population level are associated with benefit by way of asthma reduction.

Methods

We obtained antibiotic prescribing data from BC PharmaNet, a population-based database that captures all outpatient prescribing for British Columbia, Canada (n = 4.7 million). We focused on prescriptions in children <1 and calculated prescription rate per 1,000 population per year. We obtained asthma incidence data from the BC Ministry of Health Chronic Disease Registry. Asthma case identification uses a standard case definition making use of community and hospital diagnostic codes as well as asthma drug data from BC’s universal physician billing, hospital and drug databases. We focused on age-stratified asthma incidence for children aged 1–4. The correlation between antibiotic prescription rate in children < 1 and asthma incidence in the following year was estimated using the Spearman test.

Results

Antibiotic prescribing for all age groups fell 9.5% between 1999 and 2013. The rate for infants <1 dropped 58% from 1,014 to 427 prescriptions per 1,000 population/year. Between 2000 and 2014, asthma incidence (ages 1–4) fell 26% from 27.3 (95% CI: 26.5–28.0) to 20.2 (95% CI: 19.5–20.8) per 1,000 population/year. These trends were strongly correlated: Spearman’s rho = 0.81 (P = 0.0002). The magnitude of fall in asthma incidence is slightly greater than that predicted based on calculated population attributable risk for antibiotic exposure.

Conclusion

The population health benefit from antibiotic stewardship in infants may not be confined to slowing the emergence of resistance and could include a reduced risk of asthma. As this is a population-based ecological study, a reduction in other risk factors may also have contributed to the fall in asthma incidence. This promising trend should be further studied at individual level within a large cohort study.

Disclosures

All authors: No reported disclosures.
922. Barriers to Pediatric Staff Nurse Participation in Antimicrobial Stewardship Programs (ASP) Linked to Organizational Culture
Authors: Monsees Elizabeth , Popejoy Lori , Goldman Jennifer , Jackson Mary Anne , Lee Brian R
Published: November 2018

Background

Increasing nurse engagement in Antimicrobial stewardship programs (ASP) is a national initiative. We previously reported results from a stewardship survey where nurses indicated being confident to perform ASP practices, yet identified barriers to stewardship participation. Seventeen barriers were identified, with many centered around hospital culture such as lack of inclusion in rounds, power differentials, and nurse input not actively sought. To further understand organizational and cultural barriers which may influence nursing stewardship engagement, we used responses from the Agency for Healthcare Research and Quality (AHRQ) Patient Safety survey to evaluate nursing perception on hospital culture.

Methods

Data from the 2017 AHRQ survey were used. Nurses working on noninpatient floors (e.g., post anesthesia care units) were excluded. For this analysis, we included 4 domains pertinent to stewardship initiatives: communication, information exchange, teamwork within and across units. Composite scores within each domain were calculated. Scores were stratified by Intensive Care Nursery (ICN), Pediatric Intensive Care Unit (PICU), Oncology (Onc), medical-surgical (med-surg) units, and dual units (e.g., float pool).

Results

A total of 424 nurses participated in the survey; 138 (33%) ICN, 90 (21%) PICU, 42 (10%) Onc, 168 (40%) med-surg, and 23, (5%) dual. The majority of nurses had been employed by the hospital for 0–5 years (237; 56%) with 76 (18%) having more than 15 years. The majority of nurses expressed neutrality with communication. Approximately 20% disagreed with the level of information exchange. Nurses perceived teamwork within a unit more favorably than teamwork across units. Responses were relatively consistent across units.

Conclusion

Successful ASP require interdisciplinary collaboration and communication. Barriers related to communicating and exchanging information may limit nursing engagement. Assessments already used at hospitals could potentially guide methods of integrating nurses into stewardship with AHRQ data offering another lens to assess factors influencing behaviors to steward. A thorough understanding of nurses’ perceived work climate may inform engagement strategies.

Disclosures

All authors: No reported disclosures.
925. Healthcare-Associated Legionnaires’ Disease, California, 2015–2017
Authors: Kim Janice , Rizzo Kyle , O’Malley Sean , Magro Monise , Rosenberg Jon
Published: November 2018

Background

Legionnaires’ disease (LD) causes significant morbidity and mortality to hospital patients and residents of skilled nursing facilities (SNF). In California, LD is reportable to local health departments via the California Reportable Disease Information Exchange (CalREDIE) surveillance system. Cases are classified as suspected or confirmed using Centers for Disease Control and Prevention (CDC) definitions. The California Department of Public Health (CDPH) Healthcare-Associated Infections (HAI) Program maintains a database of healthcare-associated LD (HA-LD) and consults with local public health departments for single cases and outbreaks.

Methods

We described characteristics of confirmed HA-LD cases in 2015–2017. We classified HA-LD as definite if patient had continuous exposure in a facility for 2–10 days prior to symptom onset and possible if patient had overnight exposure in a facility for a portion of 2–10 days prior to symptom onset.

Results

From 2015 to 2017, 125 (8%) of 1,554 confirmed LD cases were HA-LD. Of these, 73 (58%) were definite HA-LD and 52 (42%) were possible HA-LD. The majority of HA-LD cases (N = 99, 79%) occurred in southern California. SNF were associated with 57 cases (46%) and hospitals with 44 cases (35%); 23 cases (18%) had exposures in both SNF and hospitals during the incubation period. Among the definite HA-LD cases, 50 cases (68%) had exposures in a single SNF. The median age of patients with HA-LD was 77 years. The HAI Program consulted with 15 local public health agencies on 33 HA-LD investigations, including 7 outbreaks and 26 single-case investigations.

Conclusion

HA-LD represented a small but important percentage of LD in California; the majority occurred in SNF. To prevent HA-LD, California hospitals and skilled nursing facilities should implement water management programs, as recommended by CDC and required by the Centers for Medicare and Medicaid Services (CMS) since June 2017. Public health agencies should respond rapidly to investigate HA-LD cases and control outbreaks.

Disclosures

All authors: No reported disclosures.