bluuebunny/crossref_metadata_2025 huggingface dataset:
Inpatient plus Post-discharge Durations of Therapy to Identify Antimicrobial Stewardship Opportunities at Transitions of Care
Authors: Dyer April , Ashley Elizabeth Dodds , Anderson Deverick J , Sarubbi Christina , Wrenn Rebekah , Hicks Lauri , Srinivasan Arjun , Moehring Rebekah W
Published: October 2017

Background

In-hospital antimicrobial durations capture only a portion of total antimicrobial exposures attributable to that inpatient stay. Review of electronic discharge prescriptions could allow stewards to identify excessive prescribing durations.

Methods

We performed a retrospective review of inpatient and discharge antimicrobial prescribing at three hospitals from April to September 2016 using two data sources: electronic medication administrations and electronic prescription orders at discharge. Antimicrobial agents from the National Healthcare Safety Network Antimicrobial Use (NHSN AU) module were included. Durations were calculated for admissions in which patients received at least one dose of an antimicrobial agent on inpatient units. Intended post-discharge durations were captured in days duration fields or calculated from sig and quantity fields of discharge prescriptions. Post-discharge days and inpatient days were summed to calculate the total duration of therapy resulting from the admission. Descriptive statistics were used to describe inpatient, post-discharge, and total durations.

Results

Among 45,693 inpatient admissions, NHSN AU antimicrobials were given during 23,447 inpatient admissions (51%) and in electronic discharge prescriptions for 7,442 admissions (16%). Median total duration was 4 days (IQR 2–11) among all patients who received antimicrobials and 12 (IQR 9–17) among those who received discharge prescriptions. Common post-discharge durations were 5, 7, and 10 days (Figure 1). Post-discharge days accounted for 40% (78,195/196,792) of the total days of antimicrobial therapy. The most common discharge agents were ciprofloxacin (14%), amoxicillin/clavulanate (11%), and levofloxacin (8%). Most discharge prescriptions originated from medical (37.1%), surgical (15.6%), and hematology/oncology wards (14.5%).

Conclusion

Post-discharge days accounted for 40% of antimicrobial days related to inpatient admissions. Common post-discharge durations suggested clinicians were not counting inpatient days when completing discharge orders. Post-discharge days were feasibly captured through electronic prescribing records and could aid in targeting stewardship interventions at transitions of care.

Disclosures

All authors: No reported disclosures.
Prevent Antibiotic overUSE (PAUSE): Impact of a Provider Driven Antibiotic-Time out on Antibiotic Use and Prescribing
Authors: Thom Kerri , Tamma Pranita D , Harris Anthony D , Morgan Daniel , Dzintars Kathryn , Srinivasan Arjun , Avdic Edina , Li David X , Pineles Lisa , Cosgrove Sara E
Published: October 2017

Background

Empiric antibiotic (abx) therapy is often not readdressed after clinical progress becomes apparent and the results of diagnostic studies become available. We sought to evaluate whether an antibiotic time out (ATO) by front-line clinicians after 3–5 days of abx therapy could lead to a reduction in unnecessary abx use.

Methods

A quasi-experimental study to evaluate the impact of an ATO on decreasing abx use was performed over a 6-month base period and 9-month intervention period in 11 units across 6 hospitals in the greater Maryland region was conducted. Patients who received abx for at least 3 calendar days were eligible for study inclusion. Outcomes included days of abx therapy (DOT) per admission to cohort as well as percent of patients with a change in abx regimen on day 3–5 and appropriateness of abx regimens on days 3–5. Appropriateness of abx therapy was adjudicated by infectious diseases (ID) clinicians using prespecified criteria. Regression analysis was used to compare outcomes between the base and intervention periods.

Results

A total of 3,448 abx courses were reviewed, including 1,541 during the base and 1,907 during the intervention period. Overall DOT per cohort admission was similar between the two periods (12.7 vs. 12.2 hospital DOT per admission in the base and intervention periods, respectively, and was not statistically significant after controlling for unit and season (P = 0.18). After adjusting for season, unit, ID consultation, and comorbidities, there was a 36% increase in the odds of changing or discontinuing abx on days 3–5 in the intervention period compared with the base period (48% vs. 54%, P < 0.05). Similarly, there was an 89% increase in the odds of receiving an appropriate abx regimen on days 3–5 in the intervention period compared with the base period (53% vs. 68%, P < 0.01). There was no difference in the rate of Clostridium difficile lab-events in the two study periods.

Conclusion

In this multicenter study, we found that performance of an ATO by front-line providers was effective at improving the appropriateness of abx therapy 3–5 days after initiation, but did not change the amount of abx use, suggesting that additional interventions, perhaps later during hospitalization or at discharge, are needed to impact duration of abx therapy.

Disclosures

All authors: No reported disclosures.
Perinatal Case Fatality Rate Related to Congenital Zika Syndrome in Brazil: a Cross-Sectional Study
Authors: Queiroz Igor Thiago , Da Silva Maia Jessika Thais , Rosa Gleysson , Mendes Tatyana Vidal , Vidal S Jayne Alves , Lins Maria Goretti , Zacarkim Marcelo Rodrigues , Aronoff David , Labeaud A Desiree , Mendes Neto Nilson N
Published: October 2017

Background

Many studies have demonstrated a causal link between Zika virus (ZIKV) infection, microcephaly (MCP), and other congenital abnormalities (CA). This study aimed to determine perinatal case fatality rate in cases of Congenital Zika Syndrome (CZS) in the Rio Grande do Norte State (RN), a Brazilian Northeast State highly impacted by the Zika virus outbreak.

Methods

A cross-sectional study was conducted using data obtained through the State Health Department (SHD) for cases of MCP and CA in Rio Grande do Norte from April 2015 to February 5, 2016. Definition of perinatal period: commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth.

Results

During the study period, there were 486 cases of MCP and others CA notified in RN, of which 142 were confirmed and 108 remain under investigation. The remaining 236 cases have been ruled out by presenting normal examinations or due to presenting microcephaly by noninfectious causes. Of the total confirmed cases, 26.7% (38/142) died after birth or during pregnancy. 15.78% (06/38) of confirmed deaths had ZIKV infection during pregnancy and 2.63% (01/38) had a positive TORCH blood test. The six cases related to ZIKV were confirmed by RT–PCR and/or IgM/IgG antibodies against ZIKV. The remaining cases of deaths remain either under investigation or have been ruled out.

Conclusion

This study highlights a high rate of perinatal lethality (15.78%) in cases of CZS. Despite the growing number of CZS cases, the real incidence and prevalence might be higher due to the underreporting and lack of resources for confirmatory diagnostic tests (laboratory and imaging). Due to the high rate of lethality and the ongoing uncontrolled ZIKV outbreak, this study predicts an increase in the infant mortality rate in Brazil and highlights the need for developing public health programs to control the ZIKV outbreak.

Disclosures

All authors: No reported disclosures.
Fetal and Postnatal Brain Imaging for the Detection of ZIKV Encephalopathy in the Fetus/Newborn
Authors: Mulkey Sarah , Vezina Gilbert , Fourzali Yamil , Bulas Dorothy , Arroyave-Wessel Margarita , Cristante Caitlin , Swisher Christopher , Kousa Youssef , Cure Carlos , DeBiasi Roberta , Plessis Adre Du
Published: October 2017

Background

Up to 15% of pregnancies complicated by maternal ZIKV infection result in Zika-virus associated brain abnormalities in the fetus/newborn. Fetal ultrasound (feUS) is the standard imaging modality for the evaluation of fetal anatomy and for brain changes from congenital infection. Fetal MRI (feMRI) may be a useful adjunct.

Methods

We performed a prospective longitudinal neuroimaging study of fetuses/newborns of pregnant women with clinical and/or lab confirmed (RT-PCR and/or IgM/PRNT) diagnosis of Zika infection in Barranquilla, Colombia (endemic) and in Washington, DC, USA (travel-related). Gestational age (GA) at exposure and timing between ZIKV exposure/symptoms and imaging was documented. Subjects had one to two feMRIs and feUS, depending upon GA at enrollment. The feMRI and feUS protocols were standardized between sites and studies were centrally interpreted at Children’s National. Postnatally, infants received an unsedated brain MRI and head US.

Results

Forty-eight, ZIKV exposed/infected in first or second trimester pregnant women were enrolled (46 Colombia, 2 USA). Subjects had symptoms of ZIKV infection at mean of 8.4±5.7 week GA. The first feMRI and feUS were performed at 25.1±6.3 week GA. Thirty-six infants had a second feMRI and feUS at 31.1±4.2 week GA. Three of 48 (6%) cases had an abnormal feMRI: (1) heterotopias and abnormal cortical indent; (2) parietal encephalocele and Chiari II; (3) thin corpus callosum, dysplastic brainstem, temporal cysts, subependymal heterotopias, and generalized cerebral/cerebellar atrophy. FeUS in these three cases found (1) normal study; (2) parietal encephalocele and Chiari II; (3) significant ventriculomegaly with decreasing percentiles of head circumference from 32 to 36 week GA (38% to 3.6%). Postnatal head US revealed findings not seen on feUS: choroid plexus or germinal matrix cysts in nine infants and lenticulostriate vasculopathy in one infant.

Conclusion

FeMRI and feUS provide complimentary information in the assessment of fetal brain changes in ZIKV. In cases of abnormal brain structure, feMRI reveals more extensive areas of brain damage than is seen by US. Further studies are needed to determine whether cystic changes on postnatal head US are related to ZIKV infection, or are incidental findings.

Disclosures

All authors: No reported disclosures.
Maternal Immunization with a Single-Cycle Herpes Simplex Virus (HSV) Candidate Vaccine, ΔgD-2, Protects Neonatal Mice from Lethal Viral Challenge
Authors: Kao Carol , Burn Clare , Jacobs William R , Herold Betsy C
Published: October 2017

Background

Perinatal HSV is associated with ~60% mortality if untreated and with substantial morbidity even with appropriate therapy. We recently engineered a single-cycle virus deleted in glycoprotein-D (ΔgD-2) that induces high-titer antibodies (Abs) that are non-neutralizing but activate the Fc receptor (FcR) to elicit antibody-dependent cellular cytotoxicity (ADCC). Immunization with ΔgD-2 completely protects adult mice from HSV-1 and HSV-2 disease following vaginal, skin, intraocular, or intranasal challenge and prevents the establishment of latency (ELife, 2014, JCI Insight, 2016). Thus we hypothesize that maternal immunization with ΔgD-2 and/or passive transfer of immune serum will protect neonates from HSV.

Methods

Four- to 6-week-old C57Bl/6 female mice were primed and boosted at 3-week intervals with ΔgD-2 or an equal volume of uninfected cell lysates (VD60 cells). Two weeks post-boost, mice were mated and pups were challenged with a lethal dose of HSV-1 (Bx31.1) at day 7 of birth. To differentiate the contribution of transplacental vs. colostrum Abs, mothers were switched at birth. Alternatively, 7-day-old mice born to nonimmunized mothers received a single dose of immune serum (400 μg total Ab) intraperitoneally at time of intranasal challenge.

Results

Thirty-eight of 47 (81%) of the pups born to and nursed by ΔgD-2-immunized mothers survived, exhibited little or no signs of disease and were protected from latency as measured by quantifying HSV DNA by PCR in neuronal tissue. In contrast, 12/14 (86%) of pups born to control vaccinated and nursed mice developed neurological signs of disease and died (P < 0.0001, Fisher’s exact test). Survival was associated with increased ADCC Abs in the serum of neonatal mice. In contrast, passive transfer of immune serum, which consistently protects adult mice from infection, did not protect neonates. If newborns born to immunized mice suckled with control mice, protection was partially abrogated (11/19, 58% survival), suggesting that both systemic and mucosal Abs are required for complete protection.

Conclusion

Maternal vaccination with ΔgD-2 provides significant protection against intranasal neonatal challenge but may require exposure to systemic and mucosal Abs.

Disclosures

W. R. Jacobs Jr., xvax: Scientific Advisor, Research support; B. C. Herold, X-vax: Grant Investigator, Research grant and Research support
Evidence for Cross-species Influenza A Virus Transmission within Swine Farms, China
Authors: Ma Mai-Juan , Wang Guo-Lin , Anderson Benjamin , Bi Zhen-Qiang , Lu Bing , Wang Xian-Jun , Wang Chuang-Xin , Chen Shan-Hui , Qian Yan-Hua , Song Shao-Xia , Li Min , Lednicky John A , Zhao Teng , Wu Meng-Na , Cao Wu-Chun , Gray Gregory
Published: October 2017

Background

Our understanding of the risk factors for swine influenza A virus transmission between humans and pigs is sparse.

Methods

Beginning in 2015, we used a One Health approach and serial sampling to prospectively study 299 swine workers and 100 controls, their 9000 pigs, and six pig farm environments in China for influenza A viruses (IAVs) using molecular, culture, and immunological techniques. Study subjects were closely monitored for influenza-like illness (ILI) events.

Results

Upon enrollment, swine workers had higher serum neutralizing antibody titers against swine H1N1 and higher nasal wash total IgA and specific IgA titers against swine H1N1 and H3N2 viruses. Over a period of 12 months, IAVs were detected by qRT-PCR in 52 (12%) of 432 environmental swabs, 275 (7.6%) of 3600 pig oral secretion, 25 (5.8%) of 432 water, 24 (5.5%) of 432 aerosol, and 20 (4.6%) of 432 fecal-slurry specimens. Five (15.6%) of 32 subjects with ILI events had nasopharyngeal swab specimens that were positive for IAV and 17 (53%) demonstrated 4-fold rises in neutralization titers against a swine virus. Reassorted Eurasian avian-like swine H1N1, pdm09(H1N1)-like virus, and swine-like H3N2 viruses were identified in pig farms. The H1N1 viruses were nearly genetically identical with the human H1N1 viruses isolated from the subjects with ILI.

Conclusion

There was considerable evidence of A(H1N1)pdm09-like, swine H1N1 and swine H3N2 viruses reassorting and circulating within the pig farms and crossing species. These data suggest that stronger surveillance for novel influenza virus emergence within swine farms is imperative.

Disclosures

All authors: No reported disclosures.
Vaccine waning and mumps re-emergence in the USA
Authors: Lewnard Joseph , Grad Yonatan H
Published: October 2017

Background

Following decades of declining mumps incidence amid widespread vaccination, the US has experienced a resurgence in mumps cases since 2006 driven largely by outbreaks on college campuses. The occurrence of cases among previously-vaccinated individuals and in communities with high vaccine coverage has prompted concerns about performance of the live attenuated mumps vaccine (Jeryl Lynn strain) currently included in the measles-mumps-rubella (MMR) series. It is unclear whether the resurgence is due to antigenic changes in circulating mumps virus, which would warrant consideration of a new vaccine, or to waning vaccine-derived protection, necessitating additional booster doses.

Methods

We pooled data from studies of vaccine effectiveness to test for waning of protection. We used mathematical models to measure changes in population immunity since mumps vaccine introduction and to assess whether recent mumps transmission dynamics are consistent with hypotheses of waning immunity or vaccine escape.

Results

We estimate that vaccine-derived protection persists, on average, 29 (95% CI: 17–54) years after receipt of the last dose (Fig. 1). This waning accounts for 66.4% of unexplained variation in estimates of mumps vaccine effectiveness across published studies. Changes in age-specific susceptibility due to vaccine waning and declining transmission track with the current resurgence in cases among young adults in the USA, and explain outbreaks reported among vaccinated adolescents during the late 1980s (Fig. 2). In contrast, vaccine escape would not be expected to result in cases following the observed age distribution (Fig. 3). Routine adult booster vaccination is needed to sustain mumps elimination.

Conclusion

The resurgence of mumps in the USA since 2006 is attributable to waning of vaccine-derived immunity, suggesting the need for booster doses in adulthood. Trials are needed to assess clinical protection afforded by booster doses in individuals with a history of MMR vaccination.

Disclosures

J. Lewnard, Pfier: Grant Investigator, Research grant
Retail Meat as a Potential Transmission Source of Community-Acquired Urinary Tract Infection
Authors: Yamaji Reina , Rubin Julia , Friedman Cindy , McDermott Patrick , Hung-Fan Melody , Riley Lee
Published: October 2017

Background

Escherichia coli causes approximately 80% of community-acquired UTI (CA-UTI), but the sources of these uropathogenic E. coli infections are not well established. Recent studies have suggested that food, especially poultry, may serve as a source of UPEC. Here we prospectively examined E. coli isolates from patients with CA-UTI and retail meat concurrently available from the same geographic region to determine the frequency of shared genotypes.

Methods

Between September 2016 and May 2017, we collected urine samples from patients with UTI examined at a university-affiliated healthcare center. During the same time, we recovered E.coli from retail meat products (chicken breast, ground turkey, ground beef, and pork chops) collected as part of the National Antimicrobial Resistance Monitoring System (NARMS) FDA retail meat sampling program in Northern California. Urine samples and buffered peptone water containing meat samples were cultured on MacConkey agar. Lactose-positive and indole-positive colonies were presumptively identified as E coli. Bacterial DNA was extracted by a freeze-boil method. E. coli isolates were genotyped by multilocus sequence typing (MLST).

Results

Of 1020 urine samples, E. coli was isolated from 210 (21%). Five pandemic MLST genotypes (ST95, ST127, ST69, ST73, and ST131) accounted for 126 (60%) isolates. Of 200 meat samples, E. coli was isolated from 76 (38%). E. coli was isolated from 29 (73%) of 40 ground turkey samples, 34 (43%) of 80 chicken breast, 7 (18%) of 40 ground beef, and 6 (15%) of 40 pork chop. ST69 and ST131 were isolated from 3 chicken samples. Other genotypes of E. coli isolates from meat samples and CA-UTI included ST10 (3), ST38 (2), ST88 (1), ST117 (5), ST906 (1), and ST1844 (1). Eleven (32%) of 34 chicken samples contained UPEC strains, compared with 4 (14%) of 29 ground turkey samples, and 1 (17%) of 6 pork chop samples; no beef samples contained UPEC strains.

Conclusion

Overall, we found that nearly one-quarter of retail poultry products that we tested contained UPEC strains with the same MLST genotypes found in CA-UTI patients. Foodborne transmission may account for a substantial proportion of CA-UTI. Additional studies are needed to demonstrate transmission of these genotypes from poultry to patients and to target possible prevention measures.

Disclosures

All authors: No reported disclosures.
Pharmacodynamic Target Attainment for Meropenem and Piperacillin/Tazobactam Using a PK/PD-based Dosing Calculator in Critically Ill Patients
Authors: Heil Emily , Nicolau David P , Robinson Gwen , Farkas Andras , Thom Kerri
Published: October 2017

Background

Unbound plasma concentrations of β-lactam antibiotics vary widely and attainment of PK/PD targets is highly variable in critically ill patients, which may affect microbiologic cure or contribute to toxicity. PK/PD-based antibiotic dosing programs may provide more accurate doses that achieve predicted targets for a cultured organism.

Methods

This was a single center, prospective study of critically ill patients with culture positive gram-negative infections treated with meropenem (MEM) or piperacillin/tazobactam (TZP). A PK/PD-based antibiotic dosing app was used to select doses that had a probability of target attainment (PTA) of 90% or greater for time above MIC (fT>MIC) of at least 40% for MEM and 50% for TZP. Total meropenem, piperacillin and tazobactam mid-point and trough concentrations were obtained at steady-state and adjusted for protein binding, to assess target attainment.

Results

Thirty-six patients were enrolled; 20 received MEM and 16 TZP. Antibiotic concentrations varied widely amongst patients, particularly with TZP. MEM and TZP concentrations are displayed in Table 1 and Figure 1. Doses evaluated for >90% probability of target attainment in the dosing calculator differed from standard package labeled doses for 25% (5/20) of MEM and 18.8% (3/16) of TZP patients. All (20/20) MEM and 94% (15/16) TZP patients maintained fT>MIC for the entire dosing interval.

Conclusion

A PK/PD based antibiotic dosing calculator that provides individualized β-lactam doses can lead to altered doses that may increase probability of target attainment in critically ill patients. Future research is needed to review the relevance of PK/PD-based dose adjustments on clinical outcomes.

Disclosures

D. P. Nicolau, Shionogi & Co.: Research Contractor, Research support; A. Farkas, Optimum Dosing Strategies: Employee, Salary.
Communicating Microbiology Results. It’s Not Just What You Say, But How You Say It
Authors: Musgrove Mary , Kenney Rachel M , Kendall Ronald , Tibbetts Robert , Samuel Linoj , Peters Mike , Davis Susan
Published: October 2017

Background

Gaps in microbiology communication can lead to suboptimal antibiotic prescribing. In May 2016, our laboratory modified reporting of respiratory cultures growing commensal flora only to specify “no methicillin-resistant Staphylococcus aureus/MRSA or Pseudomonas aeruginosa” (PA). The purpose of this study was to compare MRSA and PA antibiotic therapy utilization before and after the change.

Methods

IRB approved, quasi-experiment at four hospitals with an antimicrobial stewardship program. Dates: August 1, 2015–January 31, 2016 and August 1, 2016–January 31, 2017. Included: ≥18 years, commensal flora only respiratory culture, empiric MRSA and PA antibiotic for treatment of lower respiratory infection. Excluded: non-respiratory infection. Primary outcome: MRSA or PA therapy de-escalated. Secondary outcomes: time to culture result, MRSA and PA antibiotic days of therapy, length of stay. Safety outcomes: acute kidney injury (AKI), C. difficile (CDI), subsequent multi-drug-resistant organism (MDRO), in-hospital all-cause mortality.

Results

Two hundred and ten patients included, 105 per group. Median age 64 and 61 years, male sex 52% and 56% in pre- and post-group, respectively. Empiric antibiotics, pre vs. post: vancomycin 94% vs. 95%; cefepime 66% vs. 36%; piperacillin–tazobactam 10% vs. 46%. MRSA or PA antibiotics de-escalated: 39% pre and 73% post (P < 0.001). See Table 1 for variables associated with antibiotic de-escalation. Days of therapy: 7 vs. 5 days (P < 0.001). AKI 31% vs. 14% (P = 0.003). Eight subsequent MDRO in pre and one in post (P = 0.035). No differences: time to culture result, length of stay, mortality, CDI.

Conclusion

Improved microbiology communication to assist prescriber interpretation of commensal respiratory flora was associated with a reduction in the proportion of patients that received antibiotics targeting MRSA and PA.

Disclosures

S. Davis, Merck: Received grant through college that I’m faculty for, Grant recipient; Allergan: Speaker’s Bureau, Consulting fee; Allergan: Consultant and Scientific Advisor, Consulting fee; Medicines Company: Consultant and Scientific Advisor, Consulting fee; Zavante: Consultant and Scientific Advisor, Consulting fee.
Can antibiotic De-escalation Be Measured Without Chart Review? A Proposed Electronic Definition
Authors: Moehring Rebekah W , Ren Xinru , Anderson Deverick J , Davis Angelina , Dyer April , Lokhnygina Yuliya , Hicks Lauri , Srinivasan Arjun , Ashley Elizabeth Dodds
Published: October 2017

Background

Antimicrobial stewardship programs promote de-escalation: moving from broad to narrow spectrum agents and/or stopping antibiotics as more clinical data return. A standard definition of de-escalation objectively applied to electronic data could provide a means to assess stewardship improvement opportunities.

Methods

We performed a retrospective cohort study of de-escalation events among five hospitals from the Duke Health System and the Duke Antimicrobial Stewardship Outreach Network using 2016 electronic medication administration record data. Antibiotics were ranked into four categories: narrow spectrum (e.g., cefazolin), broad spectrum, extended spectrum, and agents typically targeted for protection (e.g., meropenem). Included patients were cared for on inpatient units, had antibiotic therapy for at least 2 days, and had at least 3 days of hospitalization after starting antibiotics. De-escalation was defined as reduction in either the number of antibiotics or rank measured at two time points: day 1 of initiation of antibiotic therapy and day 5 (or day of discharge if occurring on day 3 or 4). Escalation was an increase in either number or rank of agents. Unchanged was either no change or discordant directions of change in number and rank. For all categories, the outcome was percent among qualifying admissions. Descriptive statistics were used to describe de-escalation among hospitals, unit type, and ICD-10 diagnoses.

Results

Among 39,226 included admissions, de-escalation occurred in 14,138 (36%), escalation in 5,129 (13%), and antibiotics were unchanged in 19,959 (51%) (Figure). Percent de-escalation was significantly different among hospitals (median 37%, range 31–39%, P < .001). Infectious diagnoses with lower rates of de-escalation included intra-abdominal infection (23%), skin and soft-tissue infection (28%), and ENT/upper respiratory tract infection (19%). Intensive care units had higher rates of both de-escalation and escalation (43% and 16%) when compared with non-ICU wards (35% and 13%, P < .001).

Conclusion

We provided an objective, electronic definition of de-escalation and demonstrated variation among hospitals, units, and diagnoses. This metric may be useful for assessing stewardship opportunities.

Disclosures

All authors: No reported disclosures.
The Role of Negative Methicillin-Resistant Staphylococcus aureus Nasal Surveillance Swabs in Predicting the Need for Empiric Vancomycin Therapy
Authors: Chotiprasitsakul Darunee , Tamma Pranita D , Gadala Avinash , Cosgrove Sara E
Published: October 2017

Background

The role of MRSA nasal surveillance swabs in guiding decisions about need for subsequent vancomycin therapy is unclear. Our objectives were to (1) determine the likelihood that patients with negative MRSA nasal swabs went on to develop MRSA infections during the same hospitalizations to assess if vancomycin therapy could be avoided once the nasal swab result returns negative, (2) assess days of vancomycin that potentially could be avoided, and (3) identify risk factors for having a negative MRSA nasal swab and developing an MRSA infection during the hospital stay.

Methods

This retrospective cohort study was conducted at six intensive care units (ICUs) at a tertiary care hospital in Baltimore from December 2013 to June 2015. MRSA nasal swabs are obtained at the time of admission and weekly thereafter for all ICU patients. The negative predictive value (NPV), defined as the ability of a negative MRSA nasal screening test to correctly predict no subsequent MRSA infection during the hospital stay, was calculated, accounting for the 3-day turnaround time of MRSA nasal surveillance swabs. Days of vancomycin therapy started or continued after 3 days from the first negative MRSA nasal swab were determined by chart review. A matched case–control study was performed to identify risk factors for patients with negative MRSA surveillance cultures who subsequently developed MRSA infections.

Results

Of 11,441 MRSA-nasal swab negative patients, the proportion of subsequent incident MRSA infections was 0.2%. Negative MRSA surveillance swabs had an NPV of 99.4% (95% CI 99.1–99.6%). Among 4,091 MRSA-negative patients receiving vancomycin, vancomycin was started or continued after 3 days since the first MRSA-negative nasal swab in 1,434 patients (35%), translating to 7,377 potentially avoidable vancomycin days. The matched case–control analysis did not identify risk factors associated with subsequent MRSA infection.

Conclusion

At our institution with robust infection control practices and low nosocomial MRSA transmission rates, patients with negative MRSA nasal swabs have a very low likelihood of subsequent MRSA infection during hospitalizations. MRSA nasal swabs can provide useful information when determining whether to initiate or stop empiric vancomycin.

Disclosures

All authors: No reported disclosures.
Doing the Same with Less: A Randomized, Multinational, Open-Label, Adjudicator-Blinded Trial of an Algorithm vs. Standard of Care to Determine Treatment Duration for Staphylococcal Bacteremia
Authors: Holland Thomas L , Boucher Helen W , Raad Issam , Anderson Deverick J , Cosgrove Sara E , Aycock Suzanne , Baddley John W , Chow Shein-Chung , Chu Vivian H , Cook Paul P , Corey G Ralph , Daly Jennifer S , Hachem Ray Y , Chaftari Anne-Marie , Horton James M , Jenkins Timothy C , Gu Jiezhun , Levine Donald P , Miro Jose M , Riska Paul , Rubin Zachary A , Rupp Mark E , Schrank John , Sims Matthew , Wray Dannah , Zervos Marcus J , Fowler Vance
Published: October 2017

Background

The appropriate duration of antibiotics for staphylococcal bloodstream infection (BSI) is unknown. An algorithm to identify patients with staphylococcal BSI who can be safely treated with shorter courses of therapy would improve care and reduce total antibiotic use.

Methods

Adult patients with staphylococcal BSI were randomized to treatment based on algorithm-based therapy (ABT) or to standard of care (SOC). Co-primary outcomes were clinical success, as determined by a blinded Adjudication Committee, and serious adverse event (SAE) rates. The prespecified secondary outcome measure was antibiotic days by treatment group, among patients without complicated BSI. Prespecified durations of therapy in ABT were: S. aureus BSI (SAB): uncomplicated: 14 days; complicated: 4–6 weeks. Coagulase-negative staphylococci BSI (CoNSB): simple (1 positive blood culture) (0–3 days), uncomplicated (>1 positive blood culture) (5 days), complicated (7–28 days). Outcomes were compared using intention-to-treat principles. The target sample size was 500 patients, to ensure 90% power for establishing noninferiority within a margin of 15%.

Results

Between April 2011 and March 2017, 509 adults with suspected staphylococcal BSI at 16 sites in the US and Spain were randomized to ABT (N = 255) or SOC (N = 254). There were 116 patients with SAB (23%) and 385 (76%) with CoNSB (Figure 1). Overall success rate in the ABT group was 82.0% vs. 81.5% in the SOC group, difference 0.5%, 95% CI −5.2% to 6.1%. SAEs were reported in 32.9% of ABT vs. 28.3% of SOC patients (OR 1.2, 95% CI 0.9 to 1.8). Among evaluable patients without complicated BSI, mean duration of therapy was 4.4 days in the ABT group vs. 6.4 days in the SOC group (difference −2.0 days, 95% CI −3.3 to −-0.7, P = 0.003). Among patients with uncomplicated SAB, treatment durations were similar (15.3 days in ABT vs. 16.3 days in SOC, difference −1 day, 95% CI −3.89 to 1.91, P = 0.497), whereas for uncomplicated CoNSB, duration was shorter in the ABT group (5.3 days in ABT vs. 8.4 days in SOC, difference −3 days, 95% CI −4.87 to −1.34, P < 0.001).

Conclusion

The use of a treatment algorithm for staphylococcal BSI was associated with significant reductions in duration of antibiotic therapy in patients without complicated BSI, without significant differences in overall success or SAEs.

Disclosures

V. Fowler Jr., NIH: Investigator, Contract HHSN272200900023C
Tracking an Unusual Carbapenemase-producing Organism from Drains to Patient Using Whole Genome Sequencing
Authors: Ramsburg Amanda M , Weingarten Rebecca A , Conlan Sean P , Dekker John P , Michelin Angela V , Odom Robin T , Bordner MaryAnn , Zellmer Caroline J , Henderson David K , Segre Julia A , Frank Karen M , Palmore Tara N
Published: October 2017

Background

The NIH Clinical Center conducts patient and environmental surveillance for carbapenemase-producing organisms (CPO). Previous investigation revealed that sink drains can become colonized with CPO. Subsequent surveillance targets included potential aqueous reservoirs, such as floor drains of environmental services (EVS) closets.

Methods

Premoistened swabs were used to culture sink drains, floor drains, and equipment for CPO. Perirectal swabs were ordered monthly for all patients in non-behavioral health wards. Specimens were plated to CRE- and ESBL-selective media, and colonies identified by MALDI-TOF. The presence of the blaKPC gene was confirmed by PCR. When environmental CPO isolates were detected, EVS procedures and practices were reviewed.

Results

In June 2016, blaKPC+ Leclercia adecarboxylata was isolated from an EVS closet floor drain, and in August 2016, from drains in four additional closets. In the previous 10 years, Leclercia sp. was isolated just once from a clinical culture. In September 2016, routine surveillance revealed new-onset blaKPC+ L. adecarboxylata colonization in a stem cell transplant recipient. Investigation included 33 cultures collected from sink and floor drains, EVS equipment, and other items. EVS equipment, especially mop buckets, were identified as a likely point source due to their use in patient care areas and closets with contaminated floor drains. Among seven mop buckets sampled, one grew blaKPC+ L. adecarboxylata. Whole genome sequencing demonstrated genetic relatedness of the Leclercia isolates. Floor cleaner was changed to a disinfectant solution. Extensive decontamination of 67 EVS closets and equipment was performed urgently. No further patient or environmental cultures have grown blaKPC+ L. adecarboxylata.

Conclusion

The recovery of a highly unusual organism, rarely found in clinical specimens, that was also carrying a blaKPC+ plasmid, allowed us to detect environmental spread of this organism in the hospital. The ability to track this organism using genome sequencing provided strong evidence of the mode of spread, leading to effective remediation. No evidence-based methods exist for remediating drain contamination, which can serve as a potential reservoir for transmission.

Disclosures

All authors: No reported disclosures.
Utility of Routine Genomic Sequencing for Infection Control Surveillance
Authors: Ellison Richard T , Hoss Andrew , Mathew Jomol , Halperin Jeff , Gross Brian , Ward Doyle V
Published: October 2017

Background

Recent work indicates that comprehensive genomic sequencing can be a highly effective tool in defining the transmission of microbial pathogens. We have studied the utility of the routine use of genomic sequencing for infection control surveillance in an academic medical center.

Methods

The genomes of inpatient and emergency department isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium were sequenced. Within each species, single-nucleotide polymorphisms (SNP) were identified in the core genome for all isolates using alignment-based methods. The number of SNP differences between isolate pairs was determined and used, in combination with the patient’s electronic medical records to identify potential transmission events.

Results

Between September 2016 and March 2017, 388 S. aureus, 66 P. aeruginosa, 48 K. pneumoniae, and 29 E. faecium isolates were sequenced from 373 patients. There was variation in the distribution of SNP differences between intrapatient isolates for the four pathogens; with the least variability for E. faecium and greatest for P. aeruginosa. The majority of the bacterial isolates from separate patients appeared to be genetically unique exhibiting marked SNP differences from other isolates. There were 19 sets of isolates where the SNP variation between interpatient isolates was either comparable to that of intrapatient variation (12) and suggestive of recent transmission events, or with SNP variation somewhat greater than the intrapatient SNP variation (7) suggesting relative relatedness. Only one of the highly related sets had been previously identified by standard infection control surveillance. Likely transmissions appeared to have occurred both in the inpatient and outpatient settings, and the transmission routes were not always apparent.

Conclusion

The routine use of genomic sequencing analysis identified previously unrecognized likely transmission events within the institution’s patient population that are of relevance to infection control surveillance. This capacity should significantly enhance our understanding of the epidemiology of hospital acquired infections, and assist in developing and implementing new prevention strategies.

Disclosures

R. T. Ellison III, Philips Healthcare: Consultant and Grant Investigator, Consulting fee and Research grant; A. Hoss, Philips: Employee, Salary; J. Mathew, Philips Healthcare: Investigator, Research grant; J. Halperin, Philips Healthcare: Employee and Shareholder, Salary; B. Gross, Philips: Employee and Shareholder, Salary; D. V. Ward, Philips Healthcare: Consultant, Investigator and Research Contractor, Consulting fee, Research support and Salary
Invasive Mycobacterium abscessus Infection after Cardiac Surgery: Epidemiology and Clinical Outcomes
Authors: Baker Arthur W , Maziarz Eileen K , Lewis Sarah S , Stout Jason E , Anderson Deverick J , Smith Peter K , Schroder Jacob N , Daneshmand Mani A , Alexander Barbara D , Sexton Daniel J , Wolfe Cameron R
Published: October 2017

Background

We recently mitigated a clonal outbreak of Mycobacterium abscessus, including a large cluster of patients who developed invasive infection after exposure to heater-cooler units (HCU) during cardiac surgery. Recent studies have described a small number of Mycobacterium chimera infections linked to open-heart surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive infection from rapidly-growing mycobacteria, such as M. abscessus.

Methods

We retrospectively collected clinical data from all patients who underwent cardiac surgery at our hospital and had positive cultures for M. abscessus from 2013 to 2016. We excluded heart transplant recipients and patients who at time of diagnosis had ventricular assist devices. We analyzed patient characteristics, antibiotic treatment courses, surgical interventions, and clinical outcomes.

Results

Nine cardiac surgery patients who met the case definition developed culture-proven invasive infection from M. abscessus (Figure 1). Seven (78%) infections occurred after surgeries that included valve replacement. Median time from suspected inoculation in the operating room to first positive culture was 49 days (interquartile range, 38–115 days). Seven (78%) patients had bloodstream infections, and six (67%) patients had sternal wound infections. Six (67%) patients developed disseminated disease with infection at multiple sites. All patients received combination antimicrobial therapy. The most common majority regimen (n = 6) was imipenem, amikacin, and tigecycline. Four (44%) patients experienced therapy-limiting antibiotic toxicities (Figure 2). Seven (78%) patients were well enough to undergo at least one surgical debridement. Five (56%) patients stopped therapy due to presumed cure, but four (44%) patients had deaths attributable to M. abscessus infection.

Conclusion

Invasive M. abscessus infection after cardiac surgery was associated with high morbidity and mortality. Most patients underwent surgical debridement and received prolonged three-drug antimicrobial therapy, which was complicated by numerous antibiotic toxicities. Treatment cured five patients, but four patients died from mycobacterial disease.

Disclosures

All authors: No reported disclosures.
Respiratory Syncytial Virus bronchiolitis: Impact of second-hand smoke exposure on immune profiles
Authors: Diaz Alejandro , Cohen Daniel M , Jaramillo Lisa , Smith Bennett , Groner Judith , Ramilo Octavio , Mejias Asuncion
Published: October 2017

Background

RSV is the leading cause of hospitalization for bronchiolitis in infants and young children worldwide. Second-hand smoke (SHS) exposure has been associated with increased morbidity in children with respiratory infections. The objectives of this study were to explore the association between SHS measured by hair nicotine and disease severity in infants with RSV infection, and to define its impact on the blood transcriptional immune profiles.

Methods

Single-center, prospective study of previously healthy infants presenting to the Emergency Department with RSV bronchiolitis with and without SHS exposure assessed by hair nicotine levels. Exclusion criteria included: prematurity; chronic medical conditions, and insufficient hair. Clinical outcomes were assessed using a clinical disease severity score (CDSS; ranging from 0 to 15) and care provided (hospitalization and intensive care). Blood samples from patients and healthy controls were obtained at enrollment for gene expression profiling, and differences in profiles stratified by SHS exposure.

Results

A total of 70 infants with RSV were enrolled (median age 2.7 months; 44 (62.8%) males; 44 (62.8%) white). Hair nicotine was detected in 45 (64.2%) infants with RSV while 25 RSV+ infants had undetectable hair nicotine levels. Demographic variables were not significantly different between SHS exposed and nonexposed infants. Median nicotine concentrations in infants with severe (CDSS >10) vs. mild RSV disease (CDSS < 5) were 5.3 and 2.1ng/mg (P = 0.49). In addition, blood transcriptional profiles in RSV infants exposed to SHS vs. nonexposed, were characterized by significantly greater overexpression of genes related to inflammation, apoptosis and cell death, and greater suppression of T and B cell-related genes (Figure 1).

Conclusion

In otherwise healthy infants with RSV infection exposure to SHS was associated with greater inflammation and blunted T and B cell responses. Although not statistically significant, hair nicotine levels were higher in patients with more severe RSV bronchiolitis.

Disclosures

O. Ramilo, Abbvie: Board Member, Consulting fee; Regeneron: Board Member, Consulting fee; Janssen: Board Member and Investigator, Consulting fee and Research grant; NIH: Grant Investigator, Research grant; A. Mejias, Janssen: Investigator and Scientific Advisor, Consulting fee and Research support; Abbvie: Consultant and Scientific Advisor, Speaker honorarium; Novartis: CME lecture, Speaker honorarium; NIH: Investigator, Research grant
Predictors of Linkage to and Retention in HIV Care Following Release from Connecticut Jails and Prisons
Authors: Loeliger Kelsey B , Altice Frederick L , Desai Mayur M , Ciarleglio Maria M , Gallagher Colleen , Meyer Jaimie P
Published: October 2017

Background

One in six people living with HIV (PLH) in the USA transition through prison or jail annually. During incarceration, people may engage in HIV care, but transition to the community remains challenging. Linkage to care (LTC) post-release and retention in care (RIC) are necessary to optimizing HIV outcomes, but have been incompletely assessed in prior observational studies.

Methods

We created a retrospective cohort of all PLH released from a Connecticut jail or prison (2007–2014) by linking Department of Correction demographic, pharmacy, and custody databases with Department of Public Health HIV surveillance monitoring and case management data. We assessed time to LTC, defined as time from release to first community HIV-1 RNA test, and viral suppression status at time of linkage. We used generalized estimating equations to identify correlates of LTC within 14 or 30 days after release. We also described RIC over three years following an initial release, comparing recidivists to non-recidivists.

Results

Among 3,302 incarceration periods from 1,350 unique PLH, 21% and 34% had LTC within 14 and 30 days, respectively, of which >25% had detectable viremia at time of linkage. Independent correlates of LTC at 14 days included incarceration periods >30 days (adjusted odds ratio [AOR] = 1.6; P < 0.001), higher medical comorbidity (AOR = 1.8; P < 0.001), antiretrovirals prescribed before release (AOR = 1.5; P = 0.001), transitional case management (AOR = 1.5; P < 0.001), re-incarceration (AOR = 0.7; P = 0.002) and conditional release (AOR = 0.6; P < 0.001). The 30-day model additionally included psychiatric comorbidity (AOR = 1.3; P = 0.016) and release on bond (AOR = 0.7; P = 0.033). Among 1,094 PLH eligible for 3-year follow-up, RIC after release declined over 1 year (67%), 2 years (51%) and 3 years (42%). Recidivists were more likely than nonrecidivists to have RIC but, among those retained, were less likely to be virally suppressed (Figure 1).

Conclusion

For incarcerated PLH, both LTC and RIC as well as viral suppression are suboptimal after release. PLH who receive case management are more likely to have timely LTC. Targeted interventions and integrated programming aligning health and criminal justice goals may improve post-release HIV treatment outcomes.

Disclosures

All authors: No reported disclosures.