bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Surveillance and Rapid Whole-Genome Sequencing Detects Two Unsuspected Outbreaks of Carbapenemase-Producing Klebsiella pneumoniae in a UK Teaching Hospital
Authors: Torok Estee , Brodrick Hayley , Khokhar Fahad , Blane Beth , Polgarova Petra , Brown Joanne , Enoch David , Brown Nicholas , Summers Charlotte , Preller Jacobus , Thomson Nick , Dougan Gordon , Parkhill Julian , Peacock Sharon
Published: October 2017

Background

The increasing incidence of carbapenemase-producing Enterobacteriaceae (CPE) is a global health concern, as treatment options are extremely limited. The prevalence of CPE in UK hospitals is unknown, as national screening guidelines only recommend screening in patients considered to be at high-risk of CPE. Patients in intensive care units (ICU) are at high-risk of healthcare-associated infections caused by multidrug-resistant organisms (MDRO).

Methods

We conducted a six-month prospective surveillance study to determine the prevalence of MDRO in a UK teaching hospital ICU. Between June and December 2016, all adult patients admitted to ICU were screened for MDRO on admission, on discharge, and weekly during their ICU stay. Surveillance samples included stool or rectal swabs, urine, sputum or tracheal aspirates, and wound swabs (if wounds were present). Isolates were characterized phenotypically before undergoing whole-genome sequencing (WGS), epidemiological, and phylogenetic analyses.

Results

During the first week of the study we identified stool carriage of a multidrug-resistant Klebsiella pneumoniae strain in two patients neither of whom had recognized risk factors for CPE. Both isolates were resistant to all antibiotics tested, apart from colistin, and were PCR-positive for the blaNDM-1 gene. Enhanced surveillance by the infection control team identified four additional patients in several wards who had stool carriage (n = 3) or bloodstream infection (n = 1) with a blaNDM-1K. pneumoniae isolate. Epidemiological links were identified between these six patients. Five months later, a second outbreak of multidrug-resistant K. pneumoniae was detected, involving stool carriage by four patients on two different wards. Environmental screening identified environmental contamination with multidrug-resistant K. pneumoniae on one ward. DNA sequence analysis confirmed that a novel blaNDM-1K. pneumoniaelineage (ST78) was responsible for both outbreaks in the hospital.

Conclusion

We identified two unsuspected blaNDM-1K. pneumoniae outbreaks in patients with no recognized risk factors for CPE. This highlights the importance of prospective surveillance for MDRO in high-risk settings, such as ICUs, and supports the use of rapid WGS to support outbreak investigations in real-time.

Disclosures

All authors: No reported disclosures.
Differential Neuronal Susceptibility and Apoptosis in Congenital Zika Virus Infection
Authors: Ho Cheng-Ying , Ames Heather , Tipton Ashley , Vezina Gilbert , Liu Judy , Scafidi Joseph , Torii Masaaki , Rodriguez Fausto , duPlessis Adre , DeBiasi Roberta
Published: October 2017

Background

Zika virus (ZIKV) infection during pregnancy may result in severe neurologic injury to the fetus. The mechanisms by which ZIKV injures fetal brain are not fully characterized. Although cell culture and animal models shed valuable insight into pathogenesis, they do not fully recapitulate human disease.

Methods

To characterize the mechanism of ZIKV-induced human brain injury, we performed immunolabeling on brain tissue from a 20-week fetus with intrauterine ZIKV infection. Formalin-fixed sections of brain tissue were co-immunostained with ZIKV envelope antibody, as well as neuronal and non-neuronal lineage cell markers to assess infection within populations. Apoptosis was assessed by quantifying activated caspase 3 -positive staining cells. Minimum 3–5 random microscopic fields per brain region were photographed and quantified in an automated fashion using the ImageJ Cell Counter plug-in. GraphPad Prism and Microsoft Excel software were used for data analysis.

Results

ZIKV demonstrated a wide range of neuronal and non-neuronal tropism. However, infection rate was highest in Tbr2+ - Intermediate Progenitor Cells (IPC; 81.4±12%) and DCX+ Immature Neurons (IN; 51.5±13.9%), followed by SOX2+/ Nestin+ Neural Precursor Cells (NPC; 26.6±13.4%). NeuN+ Mature Neurons had the lowest frequency of infection (MN; 10.0±7.0 %) (Figure). Apoptosis was observed in both infected and uninfected bystander cortical neurons. A high infection frequency was also observed in non-neuronal cells (astrocytes, microglia, macrophages, lymphocytes).

Conclusion

Our study provides valuable insights into ZIKV pathogenesis in the fetus; it is the first to demonstrate differential infectivity/susceptibility of neuronal lineage cells to ZIKV, and evidence of apoptosis in and around these cells. The high frequency of ZIKV+ IPC and IN implies that that infection can be supported until the immature stage of neuronal differentiation. The resistance of mature neurons to ZIKV infection may also explain why ZIKV infection in the third trimester poses less risk of microcephaly in infants. The high infection rate of non-neuronal cells also suggests potential contribution of immune-mediated mechanisms of brain injury in the setting of congenital ZIKV infection.

Disclosures

All authors: No reported disclosures.
Impact of Prior Vaccination History on Risk of Vaccine Failure with Live Attenuated and Inactivated Influenza Vaccines in Children, 2013–14 through 2015–16
Authors: McLean Huong Q , Caspard Herve , Griffin Marie R , Gaglani Manjusha , Peters Timothy R , Poehling Katherine A , Ambrose Christopher S , Belongia Edward
Published: October 2017

Background

Prior season vaccination may influence influenza vaccine effectiveness; however, little is known about the impact of prior vaccination or vaccine type received. We assessed prior vaccination history and risk of influenza in children over 3 seasons.

Methods

Children aged 2–17 years seeking outpatient care for febrile acute respiratory illness were recruited during the 2013–14 through 2015–16 seasons (1 vaccine-mismatched H3N2 season and 2 H1N1pdm09 seasons) at 4 US sites. Influenza was confirmed by RT-PCR. Vaccination data for the season of enrollment (current) and 3 prior seasons were obtained from medical records and immunization registries. Among children who received 1 dose of influenza vaccine during the current season, risk of vaccine failure (ie, PCR-confirmed influenza) was estimated using test-negative design with logistic regression models adjusted for age, season, enrollment site, enrollment week (relative to peak), and outpatient visits. Risk of failure with live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) were modeled separately. Separate models were used for vaccine history based on number of seasons and vaccine type received (ie, none, LAIV, IIV, both).

Results

Influenza was detected in 191 (12%) of 1601 children who received 1 vaccine dose during the current season: 117 H3N2 and 74 H1N1pdm09. Among 508 current season LAIV recipients, 239 (47%) received LAIV and 144 (28%) received IIV in the prior season. Among 1093 current season IIV recipients, 94 (9%) received LAIV and 711 (65%) received IIV in the prior season. For LAIV, receipt of vaccine (any type) in a prior season was associated with a decreased risk of H3N2 failure (odds ratio 0.23; 95% CI, 0.09–0.57). Prior vaccination was not associated with risk of LAIV vaccine failure against H1N1pdm09. For IIV, there was no evidence that prior vaccination was associated with risk of vaccine failure against H3N2 or H1N1pdm09. Similar results were seen in children without any high-risk conditions.

Conclusion

Risk of vaccine failure among vaccinated children varied by vaccine type and virus subtype. Future studies should examine immunologic effects to better understand these differences.

Disclosures

H. Q. McLean, MedImmune: Grant Investigator, Research support; H. Caspard, MedImmune: Employee, Salary; M. R. Griffin, MedImmune: Grant Investigator, Grant recipient; M. Gaglani, MedImmune: Investigator, Research support; T. R. Peters, MedImmune: Investigator, Research support; K. A. Poehling, MedImmune: Investigator, Research support; C. S. Ambrose, AstraZeneca: Employee, Salary; E. Belongia, MedImmune: Grant Investigator, Research support
Impact of a Provider Communication Training Intervention on Adolescent Human Papillomavirus Vaccination: A Cluster Randomized, Clinical Trial
Authors: O’Leary Sean , Pyrzanowski Jennifer , Lockhart Steven , Barnard Juliana , Campagna Elizabeth , Garrett Kathleen , Fisher Alison , Dickinson Miriam , Dempsey Amanda
Published: October 2017

Background

Effective human papillomavirus (HPV) vaccines have been available in the US for several years but are underutilized. Provider communication about the vaccine is a key factor influencing uptake, yet effective communication tools are lacking or untested. Our objective was to evaluate the impact of a Motivational Interviewing-based 5-component provider HPV vaccine communication intervention on adolescent HPV vaccine uptake.

Methods

This was a cluster randomized controlled trial of 16 primary care practices in the Denver area that included 188 medical providers and 43,132 adolescent (11–17 years old) patients. The 5-components of the intervention included an HPV fact library to create practice-specific HPV fact sheets, a tailored parent education website, HPV-related disease images, an HPV vaccine decision aid, and 2 hours of in-person communication training on using a presumptive vaccine recommendation followed by Motivational Interviewing (MI) if parents were vaccine hesitant. Each practice participated in a series of 4 intervention development meetings over a 6 month period (8/2014 – 1/2015) before launching the intervention. Primary outcomes were differences between control and intervention practices over time (i.e., “difference in difference” (DID)) in HPV series initiation (≥1 dose), and completion (≥3 doses) among 11–17 year old patients seen between 09/01/2013-08/31/2014 and 2/1/2015-1/31/2016. Vaccination data were obtained from clinics’ records and augmented with a state immunization registry.

Results

Adolescents in the intervention practices had a significantly higher odds of HPV series initiation over time than those in control practices (DID Adjusted Odds Ratio (AOR) 1.46, 95% Confidence Interval (CI) 1.31–1.62) and completion (AOR 1.56, 95% CI 1.27–1.92). This translated into a 9.5 absolute percentage point (PP) increase in HPV series initiation, and a 4.4 PP increase in HPV series completion in intervention practices over control practices. The intervention had a greater impact in pediatric compared with family medicine practices, and in private practices compared with public.

Conclusion

Implementation of a 5-component HPV vaccine provider communication intervention significantly improved HPV vaccine series initiation and completion among adolescent patients.

Disclosures

A. Dempsey, Merck, Pfizer, Sanofi pasteur: Consultant, no research funding
Decrease in Antibiotic Sales in Brazil After New Control Legislation
Authors: Slain Douglas , Lopes-Júnior Rogerio , De Toledo Maria Inês , Del Fiol Fernando , Barberato-Filho Silvio
Published: October 2017

Background

Brazil, like many Latin American countries, has struggled with the inappropriate use of antibiotics in the community without a prescription form a physician. Since November 2010, The Brazilian Health Surveillance Agency has established stricter control of antibiotic sales, which requires that a copy of antibiotic prescriptions be retained by the pharmacy for audit. Pharmacists now also have more severe civil and criminal liability if they allow the sale of antibiotics without a prescription. The aim of this study was to analyze the impact of the new legislation preventing the sale of antibiotics in pharmacies without a prescription.

Methods

The data for antibiotic usage in units was collected from electronic monitoring of pharmacy members of the Brazilian Federation of Pharmacies (FEBRAFAR), which tracked information about the antibiotics sold in approximately 3,000 pharmacies from 1,500 municipalities across Brazil. We compared the sale of antibiotics during two time periods: 12 months prior to the new legislation and 12 months after.

Results

We observed a reduction in pharmacy sales of each class of antibiotics included in this study following the implementation of the new legislation. Pharmacy sales for 27 (84.4%) of the 32 antibiotics included in the study were reduced in response to the new legislation, whereas sales of five antibiotics were increased. Overall, tetracycline (−57.8%), co-trimoxazole (−28.8%), and amoxicillin (−29.1%) showed the largest reduction of all agents. With month to month analysis, the greatest reduction in units sold/month was observed for the following therapeutic classes: tetracyclines (30.5%), sulfonamides (28.5%), macrolides (25.0%), and penicillins (20.5%). Yearly trend analysis showed a significant reduction in antibiotics during the winter months (average monthly difference: −31.5%, P < 0.05)

Conclusion

The reduction in the number of antibiotic units sold by pharmacies after the implementation of legislation designed to regulate antibiotic use in Brazil suggests that the policy is successful and will contribute to rational use of antibiotics in Brazil.

Disclosures

All authors: No reported disclosures.
Outcomes of a Provincial Pilot Program to Reduce Unnecessary Urine Culturing and Antibiotic Overuse in Long-term Care
Authors: Brown Kevin , Chambers Andrea , Leung Valerie , Langford Bradley , Quirk Jacquelyn , Garber Gary
Published: October 2017

Background

Antibiotics are frequently prescribed for long-term care residents with asymptomatic bacteriuria, for which there is no indication. In order to help reduce unnecessary urine culturing and concomitant antibiotic use, C. difficile infection, and antibiotic resistance, Public Health Ontario (PHO) developed a multi-component organizational change program. The program focuses on five practice changes, recommends nine implementation strategies that have been linked to barriers, and includes an implementation planning process.

Methods

A purposive sampling strategy was used to recruit 12 long-term care homes (LTCHs) in the province of Ontario, Canada. LTCHs worked with PHO staff to implement the program over a 4-month period in mid-2016. The outcome evaluation compared rates of urine cultures sent, total antibiotics, and urinary antibiotics (ciprofloxacin, nitrofurantoin, TMP/SMX, and fosfomycin) per 1,000 resident days before and after the implementation phase. A Poisson regression model adjusting for time-trends, seasonality and controlling for autocorrelation, was used.

Results

Of the 12 LTCHs recruited, as of May 2017, 9 LTCHs provided data, totaling 106 facility-months. During the pre-implementation phase, inter-facility variation in urine culturing rates (mean = 2.4, inter-decile range [IDR] = 4.3), total antibiotic use (median = 3.2, IDR = 5.5), and urinary antibiotic use (median = 1.2, IDR = 2.2), were large (Figure 1). Comparing the post-implementation period to the pre-implementation period, we observed a 31% adjusted decline in urine culturing (incidence rate ration [IRR] = 0.69, 95% CI: 0.51 to 0.94, Figure 2), a 65% adjusted decline in total antibiotic use (IRR = 0.35, 95% CI: 0.13 to 0.92), and a 38% adjusted decline in urinary antibiotic use (IRR = 0.62, 95% CI: 0.23 to 1.68) across the participating facilities.

Conclusion

While there was variation in baseline urine culturing rates and antibiotic use across LTCHs, preliminary data indicate that these outcomes declined in a relatively short time period following implementation of an organizational change program. Plans to expand the program to the provinces 600 LTCHs could prioritize facilities with high baseline urine culturing rates.

Disclosures

All authors: No reported disclosures.
A population-based Study of Recurrent Symptomatic Bordetella pertussis Infections in Children in California, 2010–2015
Authors: Platt Lauren , Thun Melissa , Harriman Kathleen , Winter Kathleen
Published: October 2017

Background

Natural infection with Bordetella pertussis is thought to result in 4–20 years of immunity against subsequent symptomatic pertussis infection. However, these estimates are based on studies in unvaccinated or whole-cell vaccinated children. We conducted a population-based study of pertussis infection and reinfection during a 5-year period in California in an exclusively acellular-pertussis vaccinated cohort.

Methods

California surveillance data were reviewed to identify all children with two reported incidents of pertussis with symptom onset from January 1, 2010 through December 31, 2015. Case investigation reports were reviewed and children with at least two episodes of symptomatic pertussis infection that met the case definition were included.

Results

Of 26,259 pertussis cases reported in children <18 years, 27 children met the inclusion criteria. Recurrent cases occurred among children of all ages, and the median age for the first and second pertussis episodes were 3.5 years (range, 1.3 months-14 years) and 6.5 years (range, 5.2 months–16.3 years) respectively. The median duration of time between initial infection and reinfection was 1.3 years (range, 2.9 months–4.4 years). Twenty-one children (78%) had received ≥3 doses of DTaP vaccine at the time of their first pertussis infection, 1 (4%) had received 1 dose, and 5 (19%) were unvaccinated.

Conclusion

Recurrent cases of pertussis infection are very rare. Contrary to previous reports that natural infection with B. pertussis results in 4–20 years of sterilizing immunity, we demonstrate that symptomatic reinfection with pertussis can occur as soon as 89 days following the first infection. More research is needed to understand the immune response to B. pertussis infection in children vaccinated with acellular-pertussis vaccines.

Disclosures

All authors: No reported disclosures.
Cervical Adenocarcinoma in Situ in the United States: Results from Population-based Laboratory Surveillance, 2008–2014
Authors: Cleveland Angela Ahlquist , Johnson Michelle L , Gargano Julia W , Park Ina U , Griffin Marie R , Niccolai Linda M , Schafer Sean , Bennett Nancy M , Markowitz Lauri E , Unger Elizabeth R
Published: October 2017

Background

Cervical cancer screening methods are more effective for detection of squamous cell carcinoma precursor lesions (cervical intraepithelial neoplasia; CIN2 and 3) than for less-common adenocarcinoma precursors (adenocarcinoma in situ; AIS). Primary prevention through human papillomavirus (HPV) vaccination is expected to impact both CIN and AIS, although less data exist about the HPV types associated with AIS. We analyzed HPV types detected in AIS and CIN identified through population-based surveillance.

Methods

The Centers for Disease Control and Prevention and partners conduct surveillance for CIN2, CIN3, and AIS (CIN2+) among women aged ≥18 years in five locations in the United States. Specimen blocks for women aged 18–39 are sent to CDC for HPV typing using L1 consensus PCR. We analyzed cases with AIS only, AIS with CIN2 or 3 (AIS+CIN), and CIN3 only, the highest grade squamous cell precursor. We used chi-square tests to compare HPV types by histology. Types evaluated were HPV16 and 18 (high-risk (HR) types targeted by all HPV vaccines), 5 additional HR types targeted by the 9-valent vaccine (31/33/45/52/58; “additional 9vHPV”), and 7 other HR non-vaccine types (35/39/51/56/59/66/68).

Results

Between 2008 and 2014, 18,394 women were diagnosed with CIN2+. Of those, 517 (2.8%) had AIS (283 AIS only, 234 AIS+CIN) and 5,766 (31%) had CIN3 only. Median ages at diagnosis for AIS, AIS+CIN, and CIN3 were 37, 32, and 31 years, respectively. HPV typing results were available for 89 AIS, 99 AIS+CIN, and 2,923 CIN3 cases; HPV was detected in nearly all specimens (99% AIS, 100% AIS+CIN, 98% CIN3), and 21% of positive specimens had >1 HPV type identified. HPV16 (AIS: 51%, AIS+CIN: 64%, CIN3: 59%; p ≤ 0.001) and HPV18 (AIS: 39%, AIS+CIN: 31%, CIN3: 5%; P ≤ 0.001) were most common. Additional 9vHPV types (AIS: 3%, AIS+CIN: 12%, CIN3: 26%; P ≤ 0.001), and HR non-vaccine types (AIS: 6%, AIS+CIN2+: 2%, CIN3+: 9%; P ≤ 0.001) were detected less frequently.

Conclusion

HPV types differed by histology, with AIS having a greater proportion of HPV 18 and a lower proportion of additional 9vHPV and HR non-vaccine types. This report on the largest sample of genotyped AIS cases to date provides data for vaccine impact monitoring, and suggests a high opportunity for vaccine prevention of AIS.

Disclosures

M. R. Griffin, MedImmune: Grant Investigator, Grant recipient
Asymptomatic Lymphogranuloma Venereum among Nigerian Men who have Sex with Men
Authors: Crowell Trevor , Hardick Justin , Lombardi Kara , Amusu Senate , Odeyemi Sunday , Ivo Andrew , Baral Stefan , Nowak Rebecca , Adebajo Sylvia , Charurat Manhattan , Ake Julie , Gaydos Charlotte
Published: October 2017

Background

Among men who have sex with men (MSM), lymphogranuloma venereum (LGV) has been associated with proctocolitis that can lead to chronic complications and requires a longer course of antibiotic therapy than is recommended for infections due to other serovars of Chlamydia trachomatis (CT). We describe the prevalence and clinical features of LGV among Nigerian MSM diagnosed with anorectal CT.

Methods

MSM were recruited into the ongoing RV368 cohort in Lagos, Nigeria, using respondent-driven sampling. Participants were screened for HIV and bacterial sexually transmitted infections (STIs) every three months for up to 18 months. HIV was diagnosed using a parallel algorithm of rapid tests on fingerstick blood samples. PCR testing for Neisseria gonorrheae and CTwas performed on voided urine, oropharyngeal swab, and rectal swab specimens. For this analysis, prevalent and incident cases of rectal CT infection underwent additional testing to identify LGV serovars utilizing novel real-time PCR assays specific for the L serovars of CT Chlamydia trachomatis.

Results

From 28 April 2014–19 July 2016, 420 men underwent screening for rectal STIs, including 66 (15.7%) who had prevalent rectal infection with CT. An additional 68 participants developed incident infections during 208 person-years of follow-up. Of 134 eligible rectal swab specimens, 128 underwent further testing for LGV serovars. Seven (5.5%) of the tested samples were identified as LGV serovars of CT. None of the seven participants with LGV reported any symptoms such as fever or rectal pain. Two of the participants with LGV were simultaneously co-infected with rectal gonorrhea. HIV co-infection was common among participants with both LGV and non-LGV serovars of CT (71% and 77%, respectively, P = 0.74).

Conclusion

LGV was uncommon but present among Nigerian MSM in this study. LGV needs to be considered even in asymptomatic cases, particularly if anorectal CT infection fails to respond to the usual course of therapy. Consistent screening for L serovars of CT, or empiric treatment for LGV in cases with a high suspicion for this diagnosis, could potentially improve patient outcomes and decrease transmission.

Disclosures

All authors: No reported disclosures.
Electronic Reminder Notifications Improve Uptake of Targeted Ciprofloxacin Therapy for Neisseria gonorrheae Infections at the University of California, Los Angeles Health System
Authors: Allan-Blitz Lao-Tzu , Humphries Romney , Hemarajata Peera , Kimble Mabel , Elias Samuel , Klausner Jeffrey
Published: October 2017

Background

A wild-type gyrase A (gyrA) genotype of N. gonorrheae reliably predicts susceptibility to ciprofloxacin, which can reduce selection pressure for ceftriaxone-resistant infections, an urgent public health threat. In November 2015, UCLA Health began gyrA genotyping all N. gonorrheae positive specimens. In May 2016, we began sending reminder notifications of treatment recommendations to providers of patients with wild-type infections.

Methods

We reviewed records for all laboratory confirmed N. gonorrheae cases from November 1, 2015–April 30, 2017. Infections in different anatomic sites were considered unique infections, while unique infections in a single patient on the same date were considered a case. Empiric therapy was defined as treatment within 1 day of specimen collection. We also collected test-of-cure data among patients with wild-type infections treated with ciprofloxacin.

Results

Among 423 patients (23% HIV infected) there were 460 cases and 514 anatomic site-specific N. gonorrheae infections. Of infections, 218 (43%) had a wild-type gyrA genotype, 138 (27%) mutant, 153 (30%) indeterminate, 4 were not attempted, and 1 had missing data. There were 255 (55%) cases and 283 (55%) infections treated non-empirically. The median time-to-treatment among those cases was 4 days (interquartile range 3–6 days). Ciprofloxacin was used in 2 (3%) of 66 nonempirically treated infections prior to the start of reminder notifications, compared with 40 (18%) of 217 nonempirically treated infections after notifications began (P = 0.002). Of the 55 providers who received an email on or before the day of treatment for non-empirically treated patients, 32 (58%) used ciprofloxacin. There was no ciprofloxacin use prior to assay implementation. The trend in treatment by quarter among non-empirically treated infections is shown the Figure.

Among 30 patients treated with ciprofloxacin, 6 had a test of cure at one week, and all (100%; 95% CI 61%–100%) of those tests were negative for N. gonorrheae; 5 were from urethral specimens, and 1 was from the pharynx.

Conclusion

Electronic provider notifications augmented targeted ciprofloxacin therapy for N. gonorrheae infections. Preliminary test-of-cure data are promising.

Disclosures

All authors: No reported disclosures.
Association of Hospital-Onset Clostridium difficile Infection Rates and Antibiotic Use in US Acute Care Hospitals, 2006–2012: An Ecologic Analysis
Authors: Kazakova Sophia , Baggs James , McDonald Lawrence , Yi Sarah , Hatfield Kelly , Guh Alice , Reddy Sujan , Jernigan John A.
Published: October 2017

Background

This study investigated the association between facility-level rates of hospital-onset CDI (HO-CDI) and inpatient antibiotic use (AU) in a large group of U.S. acute care hospitals over a 7-year period.

Methods

We used adult discharge and antibiotic use data from 552 acute care hospitals participating in the Truven Health MarketScan Hospital Database from January 1, 2006 to December 31, 2012 to determine facility-level CDI rates and AU. HO-CDI was defined as a discharge with a secondary ICD-9-CM diagnosis code for CDI (008.45) and inpatient treatment with metronidazole or oral vancomycin. The relationship between facility-level HO-CDI (HO-CDI per 10,000 patient-days (PD)) and AU (days of therapy (DOT) per 1,000 PD) was examined through multivariate general estimating equation models that accounted for the correlation between annual HO-CDI rates within a hospital. The models controlled for hospital characteristics and a facility-level rate of community-onset CDI (CO-CDI), defined as a discharge with a primary ICD-9-CM code for CDI and inpatient treatment.

Results

During 2006 to 2012, the mean HO-CDI rate was 11 per 10,000 PD (interquartile range (IQR): 5.7–14.7) and mean AU was 811 DOT/1,000 PD (IQR: 710–932). After controlling for facility-level CO-CDI and other hospital characteristics, overall AU was significantly associated with facility-level HO-CDI rate; for every 50 DOT/1,000 PD increase in AU, there was a 4.4% increase in the HO-CDI rate. Similarly, the only antibiotic classes significantly associated with HO-CDI were third- and fourth-generation cephalosporins (P < 0.0001) and carbapenems (P = 0.0011) with respective increases of 2.1% and 2.4% of HO-CDI per 10 DOT/1,000 PD increase. Fluoroquinolones and β-lactam/β-lactamase inhibitor combinations were not significantly associated with HO-CDI.

Conclusion

In this ecologic analysis of over 500 hospitals, overall antibiotic use was associated with increased rates of HO-CDI. In contrast to recent patient-level analyses in the United States and national observations in England, only third- and fourth-generation cephalosporins and carbapenems were associated with HO-CDI.

Disclosures

All authors: No reported disclosures.
Mitigating Candida auris at a Busy Community Hospital: A Quasi-Experimental Near Real-Time Approach
Authors: Lesho Emil , Bronstein Melissa , McNamara Jodi , Callahan Megan , Kwak Yoon , Campbell Jean , Vargas Roberto L , Hinkle Mary , Walsh Edward
Published: October 2017

Background

Candida auris, an emerging multidrug-resistant pathogen associated with increased mortality, can disseminate on hospital surfaces and resist disinfection. Transmission dynamics remain poorly understood at community hospitals. Immediately following identification of a C. auris infection in an unsuspected patient admitted to a semi-private room 6 days previously, we sought to limit and determine the extent of C. auris contamination at Rochester General (RG), a 528-bed hospital in New York, using available resources.

Methods

The index and roommate were placed on enhanced contact precautions and moved to private rooms. Their former room was terminally cleaned with peracetic acid/hydrogen peroxide (PAHP) and UV light. Ten high-touch environmental surfaces in the new rooms of the index and roommate, the nursing stations, and throughout the ward were sampled immediately before and after, and between daily cleaning. The nares, axillae, and groin of the index, the roommate, and all concurrent ward patients were also sampled. All patients on the involved ward were sequentially moved from their initial rooms into vacated rooms that were terminally cleaned with PAHP and UV light. Prior to the index event, RG laboratory began sending all possible C. auris isolates to the state public health laboratory for confirmation, and using PAHP for all cleaning. RG also leverages preexisting agreements with other referral laboratories to support outbreak investigations. Hand-hygiene compliance averaged 80–90% on the ward. Hospital leaders, laboratory, nursing, environmental services, and local public health personnel regularly participate in infection prevention efforts.

Results

C. auris was isolated from 3 of 132 surface samples on the eighth, nineth, and 15th day of ward occupancy, and 0 of 48 patient samples from 18 co-located patients. The index remained colonized until death on hospital Day 21. No surfaces were C. auris-positive 1 month later.

Conclusion

Compared with prior reports, dissemination at RG was limited. This, the first such quantitative assessment, illustrates how community hospitals can enhance surveillance and patient safety when formal agreements, vigilance, and multi-disciplinary and interagency teamwork exist before outbreaks occur.

Disclosures

All authors: No reported disclosures.
Safety and Efficacy of Anidulafungin in the Treatment of Invasive Candidiasis in Children
Authors: Roilides Emmanuel , Carlesse Fabianne , Leister-Tebbe Heidi , Conte Umberto , Yan Jean Li , Liu Ping , Tawadrous Margaret , Aram Jalal , Queiroz-Telles Flavio
Published: October 2017

Background

Treatment with an echinocandin is recommended as first-line therapy of patients with invasive candidiasis including candidemia (ICC). Little is known about the efficacy and safety of anidulafungin (ANID) for the management of ICC in children.

Methods

Subjects aged 1 months to 17 years with ICC were enrolled into a prospective, open-label, non-comparative, multi-center, global study (NCT00761267) to receive ANID (3 mg/kg on day 1, 1.5 mg/kg daily thereafter). An interim analysis was completed in children 2–17 years. Subjects were to receive ANID for at least 10 days up to 35 days. A central venous catheter suspected as a site of infection was to be removed. A switch to oral fluconazole could be made after day 10. Treatment was required for at least 14 days after two negative cultures separated by 24 hours. Efficacy, based on a determination of global response (combination of clinical and microbiological response), was assessed at end of IV treatment (EOIVT), end of treatment (EOT), 2- and 6-week follow-up. Safety was assessed through 6-week follow-up.

Results

In total, 48 subjects (18, 2 to <5 years; 30, 5–17 years) received at least 1 dose of ANID (mean 11 days; range 1–35 days) and were assessed for safety. Forty-seven subjects had microbiologically confirmed ICC and were evaluated for efficacy. The most common baseline pathogens were C. albicans (38%) and C. parapsilosis (26%). Forty-four (93.6%) subjects had candidemia only. Global response success rates at EOIVT and EOT were 72.3 and 74.5%, respectively. All subjects reported at least one treatment emergent adverse event (AE) with diarrhea (22.9%), vomiting (22.9%), and pyrexia (18.8%) being most frequent. Five subjects discontinued treatment due to AEs of which four [increased transaminases (2), vomiting, pruritus generalis] were considered related to ANID. All-cause mortality by the 2- and 6-week follow-up visit was 12.5 and 14.6%, respectively. Of the seven deaths during the study, one was considered related to ICC; two were related to disease progression (Ewing’s sarcoma, medulloblastoma); the remaining were related to other conditions (intracranial hemorrhage, sepsis/septic shock, and respiratory failure).

Conclusion

Anidulafungin was effective with an acceptable tolerability and safety profile in children aged 2–17 years diagnosed with ICC.

Disclosures

E. Roilides, Pfizer: Grant Investigator, Investigator, Research Contractor and Speaker’s Bureau, Grant recipient, Research grant and Speaker honorarium. H. Leister-Tebbe, Pfizer: Employee, Salary. U. Conte, Pfizer Inc.: Employee, Salary. J. L. Yan, Pfizer: Employee, Salary. P. Liu, Pfizer: Employee, Salary. M. Tawadrous, Pfizer: Employee, Salary. J. Aram, Pfizer Inc.: Employee, Salary. F. Queiroz-Telles, Pfizer: Grant Investigator, Research grant
Outcomes Comparing Initial Short vs Long Course Echinocandin Therapy in Patients with Candidemia Caused by Fluconazole Susceptible Strains
Authors: Small-Saunders Jennifer L , Loo Angela , Theodore Deborah , Singh Amrita , Sobieszczyk Magdalena , Kubin Christine J
Published: October 2017

Background

Guidelines for candidemia (CAND) treatment recommend initial echinocandin (ECHINO) therapy with transition to fluconazole (FLUC) after 5–7 days in patients with clinical stability, FLUC-susceptibility, and negative cultures; however, optimal timing for transition is unknown. In the era of rapid diagnostics and antimicrobial stewardship programs (ASP), studies are needed to evaluate the impact of earlier transition in CAND due to routinely FLUC-susceptible species.

Methods

Retrospective study of adult patients at NewYork-Presbyterian Hospital from 2012 to 2014. Inclusion criteria included ≥1 blood culture with C. albicans, C. tropicalis or C. parapsilosis, ≥1 dose ECHINO initial therapy, ≥3 days total treatment, and no prior episode of CAND within 30 days. Patients with polymicrobial bloodstream infection excluded. Patients de-escalated from ECHINO at ≤3 days (short-course; SC-ECH) were compared with those who received ≥4 days of ECHINO (long course; LC-ECH). The primary outcome was 14-day complete response (CR), defined as survival with clinical improvement and sterilization of blood cultures. Secondary outcomes included day 7 microbiological success (MicroS) and 28-day survival (SURV).

Results

76 patients included: 21 in SC-ECH, 55 in LC-ECH groups. C. albicans (58%) most common species. Majority were male (59%) with median age 64 years (IQR 49–74), 62% were in ICU at time of CAND, 50% had recent surgery. No significant baseline differences between SC-ECH and LC-ECH groups, including in PITT bacteremia score ≥4 (43% vs. 42%; P = 0.4) or median APACHE (20 vs. 20; P = 0.684). There was no difference between SC-ECH vs. LC-ECH in CR (52% vs. 49%; P = 1.0), early MicroS (81% vs. 87%; P = 0.484), or SURV (62% vs. 73%; P = 0.523). On multivariable analysis with duration of ECHINO therapy forced into the model, only PITT bacteremia score <4 remained an independent predictor of CR (OR 6.1, 95% CI 2.1, 17.9; P = 0.001).

Conclusion

In adult patients with CAND due to routinely FLUC-susceptible species, early de-escalation from ECHINO was associated with similar outcomes, including day 7 MicroS. Early de-escalation based on early species identification has the potential to be a target for ASPs to optimize antifungal therapy without compromising clinical outcomes.

Disclosures

All authors: No reported disclosures.
Epidemiology and Prognostic Factors of Non-albicans Candida species Candidemia: A Multicenter Study
Authors: Lee Yu-Lin , Liu Chun-Eng , Lin Szu-Han , Hou I-Lun , Lai Huei-Wen , Wang Fu-Der , Chuang Yin-Ching , Liu Wei-Lun
Published: October 2017

Background

The incidence of Non-albicans Candida (NAC) fungemia has increased over the past decades with high mortality rates. However, the epidemiology and prognostic factors have seldom been investigated between species of NAC.

Methods

Patients with NAC fungemia between 2011 and 2014 from five tertiary hospitals in Taiwan were enrolled. The epidemiology data and factors associated with mortality including antifungal agents were collected by a standardized case-record form. A multivariate regression model was applied to analysis the factors associated with mortality.

Results

In total, 611 non-duplicated patients were enrolled. Candida tropicalis (n = 245, 42.3%) was most common followed by Candida glabrata (n = 213, 34.9%), Candida parapsilosis (n = 106, 17.3%) and others (n = 47, 7.7%). The overall 30-day mortality of all NAC candidemia was 47.7%. C. tropicalis infection had higher 30-day mortality (54.6%) than C. glabrata (42.8%) and C. parapsilosis (36.8%) (P < 0.05). In general, Charlson Comorbidity Index (CCI), liver cirrhosis, double lumen use, and recent steroid exposure predicted a poor prognosis. Instead, central line infection was a protective factor (OR 0.42; 95% CI 0.24–0.71; P = 0.001) because removal of central line was a most effective method for infection source control. In individual species of NAC, patients with C. parapsilosis infection took advantage from favorable host factors including younger age, lower CCI, fewer steroid exposure and more from central line infection than other two species. On the other hand, though the host factors were similar between C. glabrata and C. tropicalis infection, patients with C. grabrata infection took benefit from more echinocandin or high dose fluconazole (≥10 mg/kg/day) use, which was associated lower mortality than those with usual dose fluconazole (6–10 mg/kg/day). However, the echinocandin or high dose fluconazole did not improved outcome of C. tropicalisi infection.

Conclusion

The epidemiology and prognostic factors were different among NAC species. Risk assessment and therapeutic strategy should be individualized according to species when facing the rising threat of NAC infection.

Disclosures

All authors: No reported disclosures.
The Risk Factors and the Characteristics of Fungal Endophthalmitis Following Candida Blood Stream Infection, a Case–Control Study
Authors: Kato Hideaki , Sano Kayoko , Sugiyama Yoshifumi , Sakai Risa , Samukawa Sei , Nakajima Hideaki
Published: October 2017

Background

Fungal endophthalmitis is one of the severe complications following Candida blood stream infection (Candidemia).

Methods

To analyze the risk factors of Candidemia-related fungal endophthalmitis, total 50 Candidemia cases underwent ophthalmology examination between April 2011 and March 2016 were retrospectively collected from the medical records. Ten Candidemia with endophthalmitis cases were compared with 40 Candidemia cases without endophthalmitis were reviewed to analyze the risk factors and characteristics; patients’ age, gender, causative Candida species, the presence of shock, the highest sequential organ failure assessment (SOFA) score and the predisposing factors including diabetes, steroid use, hematological malignancy, cancer, central venous catheter (CVC) placement and neutropenia.

Results

By bivariate analysis, candidemia caused by C. albicans (40% vs. 6.7%, P = 0.009), the presence of shock (36.4% vs. 15.4%, P = 0.197), CVC placement (25.7% vs. 0%, P = 0.092), and neutropenia (40% vs. 15%, P = 0.097) were found higher endophthalmitis group. By logistic regression analysis, C. albicans candidemia was only found to be a significant risk factor (adjusted odds ratio 9.41 [95% CI, 1.42–64.76]).

Conclusion

C. albicans is most responsible causative agent for candidemia-related endophthalmitis. Candidemia cases with the presence of shock, CVC placement, and neutropenia should be closely monitored to early detect Candidemia-related endophthalmitis.

Disclosures

All authors: No reported disclosures.
Phaeohyphomycosis: A 10-Year Review (2006–2016)
Authors: Sundaramoorthy Varun , Duarte Frederico , Raj Promila Mohan , Michael Joy S , Rupali Priscilla
Published: October 2017

Background

Phaeohyphomycosis is a rare infection caused by dematiaceous (pigmented) fungi, frequently reported in tropical and sub-tropical countries. Data regarding this infection is sparse and comprises mainly of case reports. This study was carried out to review epidemiology, causative spectrum, clinical features, and treatment outcomes in patients with Phaeohyphomycosis.

Methods

We reviewed 20 cases of culture proven Phaeohyphomycosis over a 10-year period at Christian Medical College, Vellore, South India.

Results

In our cohort, 16 of the 20 patients were male (80%) with an average age of 42 (range 17–66 years). Most of them (35%) were from Tamil Nadu, India and some from Bhutan and Nepal. Eighty-five percent presented with cutaneous lesions, 5% with involvement of the paranasal sinuses, and 5% each had organ involvement in brain and liver. Possible predisposing factors included type II diabetes mellitus (35%), renal transplantation (30%), long-term use of steroids (15%), and human immunodeficiency virus (5%). For all the patients, the direct microscopy and the culture positivity was 100%. The common species isolated were Cladophialophora bantiana, Cladosporium cladosporoides, Cladosporium sphaerospermum, Phialophora oxyspora, and Exophiala spinifera. Most patients (60%) received monotherapy with itraconazole. Five patients were cured, four had recurrence, one patient died (due to leukemia), and 10 were lost to follow-up.

Conclusion

Phaeohyphomycosis, though an uncommon infection, causes life-threatening disease in both the immunocompetent and immunocompromised hosts. To our knowledge, this is the largest single-centre retrospective study on Phaeohyphomycosis. Though our follow-up was sub-optimal and possible in only 50%, it was noteworthy that disease recurrence was common. Better understanding of pathogenesis and newer antifungals are needed for optimal cure of this disease.

Disclosures

All authors: No reported disclosures.
Epidemiology, Risk Factors and Outcomes of Candida Empyema: A 5-Year Single-Centered Experience
Authors: Williams Jonathan , Lanfranco Odaliz Abreu , Lemos-Ramirez Juan , Bhargava Pallavi , Alangaden George , Ramesh Mayur
Published: October 2017

Background

Candida empyema is a rare manifestation of invasive candidiasis and can occur as a result of candidemia or direct inoculation of the pleural space after thoracic or abdominal surgeries. The risk factors and outcomes of candida empyema are poorly defined.

Methods

We performed a retrospective descriptive analysis of all patients that had Candida species isolated from pleural fluid, from May 2012 to April 2017 at our institution.

Results

Sixty patients with Candida empyema were identified. Patient characteristics are shown in Table 1. The majority of patients 68% had contiguous surgery and 25% had recent solid organ transplantation most of these were lung/heart transplants. The majority isolates were non-Candidia albicans species (52%). Fifty-two patients (86.7%) received antifungals treatment for empyema: 72% received an azole and 13% received an echinoncandin. Fluconazole was the most frequent antifungal (63.3%). Mean duration of treatment was 4 weeks. Of these patients 78% underwent chest tube drainage (40% before diagnosis, 39% after diagnosis) and 22% required VATS/decortication. The overall 30-day mortality was 30%. Candidemia was noted in seven patients (11.7%). Thirty-day mortality was associated with sepsis OR 1.04–11.4, P = 0.049, history of diabetes P = 0.045 and sepsis at the time of candida isolation. A history of solid organ transplantation had a negative effect on mortality OR 0.01–1.07.

Conclusion

Candida empyema was associated with recent contiguous surgery in the majority of cases including lung/heart transplants. Candida empyema is associated with significant mortality despite antifungal treatment and drainage as was associated with sepsis syndrome and diabetes.

Disclosures

All authors: No reported disclosures.
Clinical Experience with Telavancin for the Treatment of Patients with Bone and Joint Infections: Preliminary Results from the Telavancin Observational Use Registry (TOUR™)
Authors: Sims Charles , Bressler Adam , Lacy Melinda , Osmukhina Anna , Castaneda-Ruiz Bibiana
Published: October 2017

Background

Telavancin (TLV) is a lipoglycopeptide antibacterial active against a wide range of Gram-positive pathogens, including methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA). Bone and joint infections represent a complex set of diseases requiring prolonged antimicrobial therapy and are commonly caused by Gram-positive pathogens, including S. aureus.

Methods

The Telavancin Observational Use Registry (TOUR™) is a multicenter chart review study designed to characterize infection types, pathogens, and outcomes of patients treated with TLV in clinical practice. Data from TOUR were used to characterize a subset of bone and joint patients. Clinical data including patient demographics, pathogens, outcomes, and adverse events (AEs) were analyzed. Clinical outcomes were determined by investigators’ assessment.

Results

As of March 31, 2017, data for more than 1000 patients were collected from 46 sites. Of these, 286 patients were treated for bone and joint infections. Among these 286 patients, median age was 57 years (range 18−92 years) and 27% (n = 76) were aged ≥65 years, 66% (n = 189) were male, and 84% (n = 241) were White. The median body mass index was 30.0 kg/m2 (range 19.2−62.7 kg/m2). MRSA was the most commonly isolated pathogen at baseline (38%; n = 108). The median TLV daily dose and duration of treatment were 750 mg (range 300−1500 mg) or 8.3 mg/kg (range 3.7−16.9 mg/kg) and 26.5 days (range 1−119 days), respectively. Telavancin was used as second-line therapy in 71% (n = 202) of patients, and the majority of patients (66%; n = 189) were treated as outpatients. Overall, 71% (n = 203) of patients were cured or improved to step-down therapy, 9% (n = 25) failed treatment, 10% (n = 30) had an indeterminate clinical outcome at end of therapy (EOT), and 10% (n = 28) had missing or undocumented outcomes. Among the patients who had outcome assessment (n = 258) at EOT, 79% were cured or improved to step-down therapy and 10% failed therapy. AEs were reported in 45 patients; six reported a serious AE, and 32 had AEs leading to TLV discontinuation.

Conclusion

In a real-world setting, once-daily TLV produced a positive clinical response in >70% of patients with difficult-to-treat bone and joint infections and may represent an alternative treatment option.

Disclosures

C. Sims, Theravance Biopharma US, Inc.: Investigator and Speaker’s Bureau, Research grant, Research support and Speaker honorarium. A. Bressler, Theravance Biopharma US, Inc.: Investigator, Scientific Advisor, Shareholder and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. M. Lacy, Theravance Biopharma US, Inc.: Employee, Salary. A. Osmukhina, Theravance Biopharma US, Inc.: Employee and Shareholder, RSU, Stock Options and Salary. B. Castaneda-Ruiz, Theravance Biopharma US, Inc.: Employee and Shareholder, Salary