bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of Compton cooling during an X-ray flare supports a neutron star nature of the compact object in 4U1700−37
Authors: Martinez-Chicharro M , Torrejón J M , Oskinova L , Fürst F , Postnov K , Rodes-Roca J J , Hainich R , Bodaghee A
Published: October 2017

Based on new Chandra X-ray telescope data, we present empirical evidence of plasma Compton cooling during a flare in the non-pulsating massive X-ray binary 4U1700−37. This behaviour might be explained by quasi-spherical accretion on to a slowly rotating magnetized neutron star (NS). In quiescence, the NS in 4U1700−37 is surrounded by a hot radiatively cooling shell. Its presence is supported by the detection of mHz quasi-periodic oscillations likely produced by its convection cells. The high plasma temperature and the relatively low X-ray luminosity observed during the quiescence, point to a small emitting area ∼1 km, compatible with a hotspot on an NS surface. The sudden transition from a radiative to a significantly more efficient Compton cooling regime triggers an episode of enhanced accretion resulting in a flare. During the flare, the plasma temperature drops quickly. The predicted luminosity for such transitions, ∼3 × 1035 erg s−1, is very close to the luminosity of 4U1700−37 during quiescence. The transition may be caused by the accretion of a clump in the stellar wind of the donor star. Thus, a magnetized NS nature of the compact object is strongly favoured.
Testing Stewardship: A ‘Hard Stop’ to Reduce Inappropriate C. diff Testing
Authors: Drees Marci , Dressler Robert , Taylor Kim , Ayala Jamie , Kahigian Gaynelle , Briody Carol , Stephan Brian , Singh-Patel S Rani , Noor Sajid , Eppes Stephen
Published: October 2017

Background

Patients may be over-diagnosed with C. difficile infection (CDI) due to colonization, especially if laxatives are used. We had implemented an alert to prompt providers to discontinue C. diff orders in the setting of laxative use. This initially decreased orders by about 25%, but became less effective over time. Our objective was to strengthen our C. diff testing stewardship by creating a “hard stop” to require providers to think critically about C. diff testing in the presence of laxative use or the absence of documented diarrhea.

Methods

Our two-hospital, >1100-bed community-based academic healthcare system performs all C. diff testing via PCR. We implemented our initial laxative alert, which notified providers but did not prohibit testing, in March 2015. In April 2017, we launched a new alert that fired >36 hours after admission, and assessed for documented diarrhea (>2 episodes/24 hours). If diarrhea was present, it would assess for any administered laxative within prior 24 hours. If neither criterion was met, the provider could only order C. diff testing by calling the laboratory and documenting the staff person’s name in the order; no further justification was required. We measured the number of C. diff tests completed per day, the number of calls made to lab, and CDI rates (using NHSN LabID definition). Balancing measures included monitoring oral vancomycin orders without C. diff testing, and delayed CDI diagnoses.

Results

At baseline, we observed a mean of 9 (SD, 4–14) C. diff orders daily. After initiating the hard stop alert, daily testing decreased by 30% (Fig. 1). Frequency of hospital-onset CDI dropped by 45% during first month of implementation (Fig. 2), from mean 3.6/week to 2/week. To date we have not detected delayed diagnoses or empiric treatment without testing; 18 override laboratory calls have been documented.

Conclusion

Given PCR’s high sensitivity for C. diff, testing stewardship is critical to minimize false-positive cases of CDI, which lead to inappropriate treatment, prolonged length of stay, and hospital penalties. Requiring a phone call to order C. diff testing in the setting of laxative use or minimal diarrhea effectively reduced testing, and was well-accepted by nurses and providers. To date, no adverse effects have been detected.

Disclosures

All authors: No reported disclosures.
Impact of Vancomycin Serum Trough Concentrations and Vancomycin AUC/MIC on Vancomycin Response, In-Hospital Outcomes and Acute Kidney Injury in Pediatric Staphylococcus aureus Pneumonia
Authors: McNeil Jonathon , Rosas Louie , Hulten Kristina , Mason Edward O , Kaplan Sheldon L
Published: October 2017

Background

Vancomycin AUC/MIC > 400 was initially shown to be beneficial in adults with staphylococcal pneumonia. Current practice guidelines recommend targeting serum vancomycin trough concentrations (VTC) of 15–20 µg/ml in adults with severe MRSA infection to approximate these AUC/MIC goals. Small studies have shown no benefit to VTC > 15 µg/ml in children with osteomyelitis or bacteremia. We describe the impact of VTC and AUC/MIC on outcomes of pediatric S. aureuspneumonia.

Methods

Cases of S. aureuspneumonia from January 1, 2011 to December 31, 2016 were reviewed. Patients treated with vancomycin <48 hours were excluded. Suboptimal vancomycin response (SVR) was considered any combination of duration of fever, bacteremia or ICU stay > 75%-tile, need for re-operation, or mortality. The highest VTC and AUC obtained in the first 96 hours of therapy was used in analyses. Vancomycin MIC was determined with the E-test. Acute kidney injury (AKI) was defined as a doubling of the baseline serum creatinine.

Results

Thirty-six patients were identified meeting inclusion criteria with a median age of 0.74 years. 75% of isolates were MRSA and 70.4% were USA300. 80.6% of patients were admitted to the ICU and 52.8% were intubated. No benefit was observed in terms of duration of fever, bacteremia, ICU stay, ventilator or hospital days or rates of SVR between patients with VTC > or <15 µg/ml. There were substantial increases in rates of AKI with higher VTC (66.7 vs. 24.2%, P < 0.001). Among 23 patients for whom AUC/MIC determinations were possible, none achieved an AUC/MIC >400; the median AUC/MIC = 42 (IQR: 32–51). Eighty-eight% of isolates had an MIC ≥1.5 µg/ml. There was no correlation between values of AUC/MIC and length of ICU or hospital stay or SVR (AUROC 0.45).

Conclusion

While the sample size is limiting, VTC >15 µg/ml did not provide clinical benefit to children with S. aureus pneumonia compared with lower VTC levels while at the same time predisposing to nephrotoxicity. AUC/MIC > 400 is rarely achieved in children with S. aureus pneumonia and may not be a realistic goal in this infection given the rarity with which this occurs, the frequency of high MICs and the very young age of the typical patient. Large multicenter studies are required to understand optimal vancomycin dosing and monitoring in children with invasive MRSA infections.

Disclosures

J. McNeil, NIAID, NIH: Grant Investigator, Grant recipient;  S. L. Kaplan, Allergan: Grant Investigator, Grant recipient and This grant pertains to unrelated research
Microbiology of Vertebral Osteomyelitis and Implications on Empiric Therapy
Authors: Clark Abbye , Sharma Neha , Weissman Sharon , Al-Hasan Majdi N , Derrick Caroline , Sanasi-Bhola Kamla
Published: October 2017

Background

The management of vertebral osteomyelitis (VO) includes empiric antibiotic therapy while clinical cultures are being processed. Optimal antimicrobial therapy for VO, particularly when Gram-negative (GN) organisms are involved, is an area of ongoing debate. Narrow spectrum and oral antimicrobial therapy are preferred. The objective of this study was to identify characteristics of local pathogens and to formulate an institution-specific antibiotic protocol for empiric treatment of VO.

Methods

We conducted a retrospective case series study of adults diagnosed with VO from August 1, 2010 to August 31, 2015 at Palmetto Health Hospitals in Columbia, South Carolina. Cases identified by ICD-9 codes were included in the analysis if they met clinical, imaging and microbiology, criteria.

Results

Analysis is based on 150 cases of VO with a mean age of 61 years, a male predominance (91; 61%), and an average body mass index of 29kg/m2. Comorbidities included diabetes mellitus (69; 46%), tobacco use (33; 22%), and hemodialysis (20; 13%). Thirty-seven (25%) cases had recent related injury or vertebral surgery, and 14 (9%) had prior hardware. Bone, disc, or adjacent tissue cultures were obtained in 129 (86%) of cases; 60 (40%) of these had >1 sample taken. The remaining 14% had blood cultures alone. Thirty-six cases (24%) had culture negative VO. In the remaining 114 cases, 132 organisms were isolated. A total of 111 (84%) organisms were Gram-positive cocci (GPC). Of those, the majority was Staphylococcus aureus. (66; 59%) (26/66 were methicillin-resistant), coagulase-negative staphylococci (20; 18%) and Streptococcus spp. (17; 15%). Enterobacteriaceae accounted for 13/17 Gram-negative bacilli (GNB), with only one isolate of Pseudomonas aeruginosa. Of the GNB, 11/17 were susceptible to either ceftriaxone or ciprofloxacin.

Conclusion

There was a predominance of VO due to GPC suggesting that intravenous vancomycin monotherapy may be reasonable for empiric therapy in noncritically ill patients while awaiting Gram stain and clinical culture results. Addition of either ceftriaxone or ciprofloxacin to vancomycin would increase cumulative antimicrobial coverage from 84 to 92%.

Disclosures

All authors: No reported disclosures.
A Multicenter Study on Clinical Outcomes of Infections within 200 Days of Liver Transplantation among Recipients Age 65 Years and Older
Authors: Malinis Maricar , Ngo Tue , Garcia-Diaz Julia , Taimur Sarah , Mueller Nicolas , Eid Albert , Vergidis Pascalis , Pursell Kenneth , Bhaskaran Archana , La Hoz Ricardo , Bran Andres , Lee Dong , Pouch Stephanie , Avery Robin , Baddley John W
Published: October 2017

Background

Liver transplantation is increasingly performed in patients aged ≥65 years. Per the United Network for Organ Sharing data, infections are the leading primary and contributory cause of death in older liver transplant (LT) recipients. This study aims to describe the epidemiology and outcomes of infections within the first 200 days of LT in older adults.

Methods

We performed a retrospective, observational multi-center study of patients aged ≥65 years who underwent primary LT from January 1, 2010 to June 30, 2015. Data collection included patient demographics, co-morbidities, transplant data, infection event in 200 days of LT and death. Severe infection was defined as the presence of sepsis, septic shock, or sepsis with multi-organ failure.

Results

A total of 255 patients met inclusion criteria with median follow-up of 690 days (range 1– 2095). The mean age was 67.6 years (SD 2.4). Majority were male (67%) and white (85%). Frequent indications of LT were hepatocellular carcinoma (46%) and hepatitis C (32%). The median MELD score at the time of LT was 22 (range 6–47). Only 3% of recipients received thymoglobulin for induction. Acute rejection within 200 days of LT occurred in 31 (12%); graft failure in 8 (3%); and re-transplantation in 5 (2%). One hundred twenty-seven patients (50%) developed 274 infections; 63 (25%) had 1 infection and 64 (25%) had ≥ 2 infections. Median time to first infection after LT was 26 days [IQR 9–72]. Out of 274 infections, 182 (66%) occurred in <90 days. Severe infection occurred in 40/127 (31%). Cystitis (16%), colitis (12%), and pneumonia (11%) were common. Bacterial, viral, and fungal infections were 61%, 22%, and 7%, respectively. Common bacterial pathogens were Enterococcus sp. (15%), Clostridium difficile (12%) and E. coli (8%). Thirty-five (13%) opportunistic infections (OI) occurred due to Cytomegalovirus [CMV] (26), Candida (4), Cryptococcus (3), HHV-8 (1), and Aspergillus (1). Mortality due to infection was 3%, while all-cause mortality was 12%. Frequency of discharge to sub-acute or extended care facility after infection was 23%.

Conclusion

Infections are common in this older LT cohort and occurred mainly in the early post-LT period. OIs were infrequent except for CMV. Despite concerns for immunosuppression and immunosenescence, the outcome of infection within the 200 days of LT was overall favorable.

Disclosures

All authors: No reported disclosures.
Missed Opportunities to Initiate Pre-exposure Prophylaxis in South Carolina—2013–2016
Authors: Okoye Stella , Chang Man-Huei , Weissman Sharon , Dufffus Wayne
Published: October 2017

Background

PrEP, regular use of antiretroviral medications by HIV-negative individuals to prevent new HIV infections, has not been widely adopted by some young, high-risk populations. This study investigated the characteristics and estimated percentage of newly diagnosed HIV-infected individuals in South Carolina (SC) who had visited a health care facility (HCF) while HIV-negative and missed opportunities for initiating PrEP.

Methods

We used a unique person-level identifier to link case reports from the SC enhanced HIV/AIDS Reporting System and records from a statewide all payer HCF database. The HCF data include inpatient (IP), outpatient (OP), and emergency department (ED) visits to SC facilities. Because the Food and Drug Administration approved PrEP in 2012, we analyzed data for individuals diagnosed with HIV during January 2013–September 2016 with initial CD4 count ≥500 cells (recent infection) and HC visits during 2011 through the date of diagnosis. We used the two-tailed chi-square statistics with a significant threshold of P < 0.05 in SAS to investigate the association between the absence of a PrEP prescription and patient factors including demographics, behavioral risk, visit setting (IP, OP or ED), frequency of previous visits, and residence at diagnosis.

Results

A total of 785 patients were diagnosed with recent HIV infections (initial CD4 ≥500 cell) during January 2013–September 2016. Of these, 504 (64.2%) visited an SC HCF at least once before being diagnosed, 72.4% were males, 52.4% aged <30 years, 54% were men who have sex with men (MSM) or injection drug users (IDU) and 70.2% resided in urban areas. Mean number of HCF visits before HIV diagnosis was 6.6; 84.3% had ED visits; 5.9% had IP visits; and 7.0% had OP visits. Persons of female sex, Black race, younger age and urban residence were more likely to access HCF visit before HIV diagnosis (P < 0.05).

Conclusion

We now know the characteristics and percentage (64.2%) of persons with recent HIV infections captured in two large state-wide databases in SC who missed opportunities to be screened and initiated PrEP during visits to HCFs before HIV diagnosis during 2013–2016.

Disclosures

All authors: No reported disclosures.
Programmatic Congenital CMV Universal Screening Program
Authors: Carrillo-Marquez Maria , Rohde Benjamin , Tomlinson Ryan , Blanch Jacqueline , Bradford Lana , Kim-Hoehamer Young-In , Harrison Lisa , Pace Stephen , Davis Joe , Patel Chirag , Patel Anami , Arnold Sandra R , Devincenzo John P
Published: October 2017

Background

CMV is the most common congenital infection (cCMV). Traditional identification strategies including hearing screen and physical exam are insensitive and miss affected infants. To improve identification of infected  newborns, we established a universal, institutional cCMV newborn screening program.

Methods

All newborns born or transferred to nurseries in a hospital system in Memphis, Tennessee between March 2016 and April 2017 were screened for cCMV. Infant saliva was collected on a Copan swab prior to discharge and within 2 weeks of birth. Specimens were centrally processed using a real-time CMV PCR assay (Simplexa™ CMV) (DiaSorin, Cypress CA) amplifying the UL83 gene, and the 3M Integrated Cycler. Parents received educational materials on cCMV testing and natural history prior to specimen collection. All patients with a positive screen had a full evaluation including physical exam, eye exam, hearing testing, CBC, chemistries and head ultrasound (HUS).

Results

There were 35/6,114 (0.6%) positive screens. Of 35, 16 (45.7%) were male and 5 (14%) were less than 37 weeks gestation. Thirty-one of 35 saliva specimens were collected on day 0 or 1 of life. All patients were evaluated by an infectious disease specialist at a median of 15 days of age. Confirmatory urine PCR was positive in 25/33 (76%) tested. Overall, 11/25 (44%) with confirmed congenital CMV were symptomatic. This included 28% with microcephaly and 20% with low birth weight. Six (24%) failed newborn hearing screening of one or both ears. Other abnormalities included thrombocytopenia (5%), elevated ALT (10%), elevated direct bilirubin (5%), and abnormal HUS (11/25, 44%), of which 7/11 had lenticulostriate vasculopathy and 2/11 had intracranial calcifications. Twelve infected infants had an eye examination and none had retinitis. Eleven infants were offered therapy and five were treated. Ten of 25 congenitally infected infants had audiology follow-up by 6 months with four abnormal. All infants were referred for early intervention.

Conclusion

We have demonstrated the feasibility of implementing large-scale, saliva-based cCMV screening program within one hospital system. Universal screening detected twice as many infected infants than would have targeted screening based on newborn hearing screen and growth parameters.

Disclosures

J. P. Devincenzo, AstraZeneca/MedImmune: Investigator, Research support
Infectious Disease Consultation Is Associated with Decreased Mortality with Enterococcal Bloodstream Infections
Authors: Lee Rachael A , Vo Daniel , Zurko Joanna , Griffin Russell , Rodriguez J Martin , Camins Bernard
Published: October 2017

Background

Enterococcal bloodstream infections (EBSI) have been attributed with significant morbidity and mortality. The objective of this study was to determine whether IDC is associated with improved mortality in patients hospitalized with EBSI.

Methods

This is a cross-sectional study of patients admitted to the University of Alabama Health System between January 1, 2015 and June 30, 2016 who had EBSI. Patients who died within 2 days of hospitalization were excluded. Categorical variables were analyzed with chi-square or Fisher’s exact test and continuous variables were analyzed with a t-test or Wilcoxon rank-sums test when appropriate. A P-value < 0.05 was considered significant. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for factors associated with 30-day in-hospital mortality.

Results

A total of 213 patients met the case definition. One hundred and thirty-four (63%) received IDC. Baseline patient demographics and comorbidities were similar in both groups. Patients with IDC were more likely to have repeated blood cultures (99% vs. 72%, P < 0.001), echocardiogram performed (77% vs. 46%, P < 0.001), and interventions for source control (19% vs 6%, P = 0.01). Patients without IDC were more likely to have inappropriate antibiotic treatment or no antibiotics (20% vs. 0%, P < 0.001) as well as inappropriate duration of therapy (54% vs. 10%, P < 0.001). There were no differences in the rates of recurrent bacteremia or readmission within 60 days. Patients who did not receive IDC had higher 30-day in-hospital mortality (27% vs. 13%, P = 0.02). Having an echocardiogram (OR 2.75, 95% CI 1.36–5.55), surgical intervention (OR 3.11, 95% CI 1.07–9.05) and an IV catheter (OR 3.90, 95% CI 1.39–10.88) were associated with increased likelihood of IDC while inappropriate duration of antibiotics was associated with an 87% decreased likelihood of IDC (OR 0.13, 95% CI 0.06–0.29). The strongest association observed with 30-day mortality was inappropriate duration of antibiotics (OR 4.93, 95% CI 1.93–12.61).

Conclusion

IDC was associated with reduced 30-day in-hospital mortality in patients with EBSI. Although further investigation is warranted, the results of this study suggest that early involvement of ID specialists in EBSI may lead to better outcomes.

Disclosures

All authors: No reported disclosures.
Is there Failure to Screen for Hepatitis C in Newborns Suffering from Neonatal Abstinence Syndrome?
Authors: Myers John , Smith Michael , Espinosa Claudia , Woods Charles , Duncan Scott
Published: October 2017

Background

Enormous advances in treating/curing patients suffering from Hepatitis C (HepC) infection have occurred; resulting in many states mandating screening for HepC for older individuals. Unfortunately, no protection of screening exists for newborns. In Kentucky, rates of HepC among pregnant women are the second highest within the U.S., which has been associated to high intravenous drug use. Infants born to those women are at risk of HepC infection and other conditions such as neonatal abstinence syndrome (NAS). The current study examined the rate of HepC screening in a high-risk cohort (newborns suffering from NAS) and it’s impact on policy-making for this vulnerable population.

Methods

Kentucky Medicaid records, from 2015, were obtained to develop a detailed demographic, behavioral, clinical, and diagnostic data set (n = 152,749). NAS was defined by ICD-9 code 779.5 and ICD-10 code P96.1. HepC screening was defined by CPT codes (CPT 87520 [HCV, direct probe], 87521 [HCV, amplified probe], and 87522 [HCV RNA, Quantitative] or antibody [CPTs 86803–4]). Initially a descriptive study was performed, then multiple logistic regression techniques were used to test what variables impacted the odds of not being screened for HepC.

Results

A total of 1234 newborns with NAS were identified. The majority showed signs of NAS within 24 hours (64%), were white (68%) and were admitted to the hospital for an average of 24.8 days. Only one-in-three newborns with NAS (n = 412, 33.4%) were screened for HepC. Non-Whites (OR = 1.58, 95% CI 1.45–1.71, P < 0.001) and those living in non-urban areas (OR = 1.42, 95% CI 1.28–1.56, P < 0.001) were the only study variables to significantly impact the odds of not being screened for HepC (for newborns suffering from NAS).

Conclusion

A high-risk and vulnerable population for HepC may not be getting screened for HepC and thus are being underserved by the health care system. Non-Whites and those in rural areas are the most affected. Solutions and policies need to be focused on this population and area where screening is lacking. Optimization of maternal screening for HepC is crucial in high-risk populations.

Disclosures

All authors: No reported disclosures.
Assessing The Impact of The National Healthcare Safety Network’s (NHSN’s) New Baseline on Acute Care Hospital Standardized Infection Ratios (SIRs)
Authors: Soe Minn , Nkwata Allan , Edwards Jonathan R , Dudeck Margaret , Pollock Daniel
Published: October 2017

Background

To more accurately measure the progress of healthcare-associated infection (HAI) prevention efforts, the CDC’s National Healthcare Safety Network (NHSN) surveillance system updated risk-adjustment models for computation of updated Standardized Infection Ratios (SIRs), the primary HAI summary measure by NHSN. This study sought to examine how the updated SIRs varied from the previous SIRs calculated using older baselines for acute care hospital HAIs.

Methods

We analyzed NHSN data for healthcare facility-onset laboratory-identified Clostridium difficile [CDI] and methicillin-resistant Staphylococcus aureus [MRSA] bacteremia reported in accordance with the CMS’ inpatient quality reporting program requirement. The unit of analysis was CMS certification number (CCN) facility reporting in 2015. We compared overall distributions of CCN-level SIRs (CCN-SIRs) between new risk-adjustment models using a 2015 baseline (SIR_NEW) and old models using a 2011 baseline (SIR_OLD) and tested location shift (median away from null) of pairwise differences. We also examined the magnitude of shift in SIR from old to new baseline.

Results

For each HAI, the national pooled mean SIR of the new baseline was ~1.0. For CDI, the overall distributions of CCN SIR_NEW and CCN-SIR_OLD were different, and the median of pairwise difference was away from null with CCN-SIR_NEW slightly higher. For MRSA, the SIR differences were not significant. Most CCN-SIRs (83% for CDI, 93% for MRSA) remained in the same significance category across the old and new baselines (“worse,” “better, ‘not different from national benchmark’), and few CCN-SIRs were reclassified to a less favorable category. For 75% of CCN-SIRs, their relative position in the quartile distributions of SIR_NEW and SIR_OLD remained the same. The discrepancies between SIR_NEW and SIR_OLD tended to be larger among CCNs with high SIRs.

Conclusion

The updated national pooled mean SIRs were close to 1.0, validating the potential use of new risk adjustment models and baseline as updated benchmarks for tracking CDI and MRSA prevention progress. The shifts in CCN-level SIRs between old and new baselines were not large, indicating a modest impact of new baselines at the CCN level, except among hospitals with high SIRs.

Disclosures

All authors: No reported disclosures.
Corticosteroid Use Following the Onset of Invasive Aspergillosis is Associated with Increased Mortality: A Propensity Score-Matched Study
Authors: Abers Michael , Vyas Jatin
Published: October 2017

Background

The safety of corticosteroid use (CSU) during active infection is controversial. In the invasive aspergillosis (IA) literature, CSU is typically defined using the time period prior to IA onset. Clinicians caring for patients with IA are unable to control prior CSU. The more clinically relevant question is whether CSU after IA onset is harmful.

Methods

Patients hospitalized at our institution from 2004 to 2014 with IA were retrospectively identified. CSU, defined as the average daily prednisone equivalent dose during the 7-day period following IA onset, was calculated for each patient. A CSU cut-off of 7.5mg was used to assign patients to treatment (>7.5mg) or control (<7.5mg, including no CSU) groups. A propensity score (PS) was generated to predict group assignment. Nearest neighbor matching was performed with a caliper width of 0.2. A Cox proportional hazards model was used to assess survival 6 weeks after IA onset.

Results

PS matching generated 61 matched pairs (122 patients). Baseline characteristics did not differ significantly between groups (Table). CSU was associated with increased mortality (PS adjusted hazard ratio [HR] 2.91, 95% CI 1.32–6.40). In the CSU group, a trend towards lower mortality was noted if corticosteroid dose was tapered to 7.5mg/day (HR 0.68, 95% CI 0.46–1.02).

Conclusion

CSU after IA onset is associated with increased mortality. In IA patients with CSU, efforts to reduce corticosteroid dose may be beneficial.

Disclosures

All authors: No reported disclosures.
Risk Factors Associated with Persistence of Zika Virus Nucleic Acid in Serum and Semen
Authors: Lozier Matthew , Rosenberg Eli , Doyle Katherine , Adams Laura , Klein Liore , Muñoz-Jordan Jorge , Alvarado Luisa I , Sharp Tyler , Paz-Bailey Gabriela
Published: October 2017

Background

Identifying factors associated with time-to-loss of Zika virus (ZIKV) RNA in serum and semen is important to inform diagnostic testing and prevention recommendations. CDC currently recommends RT-PCR testing of serum up to two weeks after symptom onset. We evaluated such associations among participants of the Zika virus Persistence (ZiPer) study in Puerto Rico.

Methods

Patients presenting for care with Zika-like illness and ZIKV RNA detected by RT-PCR in serum or urine (index cases) were offered study participation. Index cases’ household members were offered study participation, and those with detectable ZIKV RNA were eligible for the prospective cohort. Serum and semen were collected weekly for the first month, and biweekly thereafter for participants with detectable ZIKV RNA in any fluid and at 2, 4, and 6 months post-enrollment for all others. We used chi-squared and Fischer’s exact tests to assess if detecting ZIKV RNA in specific specimens at any point was associated with sex, age, Zika-like symptoms (rash, fever, arthralgia, or conjunctivitis), or pregnancy. We performed Weibull regression models to estimate time-to-loss of ZIKV RNA in days post symptom onset (DPO) and evaluated associations between covariates and duration of detection.

Results

Among 295 participants, 260 (88.1%) had ZIKV RNA detected in serum at any point. Participants aged ≥18 years (n = 244) had a significantly longer median time-to-loss of ZIKV RNA in serum than participants aged < 18 years (n = 50) (13.1 vs. 7.8 DPO, respectively; P = 0.003) (Figure 1). Among women aged 18–39 years (n = 60), pregnant women (n = 9) had a significantly longer median time-to-loss of ZIKV RNA in serum than non-pregnant women (n = 51) (37.4 vs. 15.5 DPO, respectively; P = 0.0005) (Figure 2). The proportion of men who had detectable ZIKV RNA in semen at any point was significantly higher among men with conjunctivitis (47 of 82) than among men without conjunctivitis (3 of 14) (P = 0.01). No other associations were significant.

Conclusion

Time-to-loss of ZIKV RNA in serum was longer among adults than children, and conjunctivitis was associated with detecting ZIKV RNA in semen. This study provides evidence that time-to-loss of ZIKV RNA is longer among pregnant women than non-pregnant women. Findings may inform the recommended period to test pregnant women for ZIKV using RT-PCR.

Disclosures

All authors: No reported disclosures.
Cancer Mortality among Persons with Human Immunodeficiency Virus Infection in New York City, 2001–2015
Authors: Ramaswamy Chitra , Westheimer Emily , Braunstein Sarah
Published: October 2017

Background

With the prolonged life-span of persons with HIV (PWH) due to anti-retroviral therapy, their cancer burden has increased. Cancer continues to be a leading cause of death among PWH. Studying cancer mortality can inform and guide the development of cancer screening and prevention strategies for PWH.

Methods

We analyzed data for all persons > = 13 years who were diagnosed with HIV from 2001 to 2015 and reported to the New York City (NYC) HIV surveillance registry (HSR). Using the HSR and the underlying cause of death obtained from the NYC vital statistics registry and the National Death Index, we examined age-specific and age-standardized mortality rates from cancer and compared time trends of deaths due to HIV-related8 cancer to deaths from non-HIV-related cancers.

Results

There were 34,190 deaths reported among 154,688 PWH of whom nearly half (n = 16,804; 49.1%) died due to HIV (excluding HIV-related cancers). Among all deaths, HIV was the leading cause, followed by cancer (both HIV and non-HIV-related) (n = 5,271; 15.4%) and cardiovascular disease (n = 3,724, 10.9%). The top three causes of non-HIV-related cancer deaths were lung cancer (n = 1,040; 19.7%), liver cancer (n = 552; 10.5%), and colorectal cancer (n = 315; 5.6%). Although the mortality rate among PWH decreased over time (24.4 to 13.9 per 1,000 person-years from 2001 to 2015), the proportion of deaths attributable to all cancers increased (10.6% in 2001 to 19.9% in 2015, p < .0001). This increase was driven by non-HIV-related cancers (6.1% of all deaths in 2001 to 15.8% in 2015, p < .0001). The mean age increased from 2001 to 2015 among the dead (46 to 56 years) and among the censored (35 to 49 years). After controlling for demographic factors, transmission risk, and last CD4 count, the hazard ratio for cancer deaths was higher among people who inject drugs (HR = 1.5; 95% CI = 1.4–1.7) and those with last CD4 count < 200 (HR = 9.3; 95% CI = 8.3–10.5).

Conclusion

Although mortality rates are decreasing in PWH, deaths due to non-HIV-related cancers are increasing. The upward trend in the mean age suggests that aging may be contributing to this increase. Routine screening for liver and colon cancers along with smoking cessation may reduce lung, liver and colon cancer deaths.

Disclosures

All authors: No reported disclosures.
Real-Time PCR Targeting Mosaic penA XXXIV for Prediction of Extended-Spectrum Cephalosporins Susceptibility in Clinical Neisseria Gonorrheae Isolates
Authors: Hemarajata Peera , Wong Lisa , Soge Olusegun , Humphries Romney , Klausner Jeffrey
Published: October 2017

Background

Antimicrobial-resistant Neisseria gonorrheae (NG) is a global public health problem, resulting in limited empirical treatment options. Due to increasing minimum inhibitory concentrations (MICs) of ESCs against NG in the US, it is critical that susceptibility to ESCs be monitored. Since few laboratories routinely perform culture and susceptibility testing for NG, there is a need for a rapid test to predict susceptibility to ESCs. More than 98% of isolates with decreased susceptibility to cefixime (CFM) in the US carry mosaic penA XXXIV. In this study, we developed a multiplex real-time PCR for mosaic penA XXXIV and previously validated gyrA to predict ESCs MICs and ciprofloxacin (CIP) susceptibility.

Methods

150 NG isolates with known cefpodoxime (CPD), CFM, ceftriaxone (CRO) and CIP MICs were obtained from Neisseria Reference Laboratory at University of Washington and CDC Antimicrobial Resistance Bank. DNA extracted from culture was used in multiplex HybProbe real-time PCR on Lightcycler 480. gyrA was genotyped by melt curve and served as internal control, while presence of mosaic penA XXXIV was detected by selective amplification.

Results

All 32 (100%) CIP-susceptible and 118 (100%) CIP-resistant isolates, as determined by Clinical and Laboratory Standards Institute breakpoints, demonstrated wild-type and Ser91 mutant gyrA genotype, respectively. Melt curve genotyping demonstrated mosaic penA XXXIV melt patterns in 66/68 (97%) isolates with at least one ESC MIC above alert value set forth by the CDC (CPD and CFM MICs ≥0.25 µg/ml; CRO MIC ≥0.125), while all 82 (100%) isolates with ESC MICs under alert values did not amplify. The first of the 2 false-negative isolates had MICs above alert values for all ESCs tested and harbored IX mosaic type, while the second one had CRO MIC above alert value and harbored XII mosaic type. Both of these mosaic types did not share homology with mosaic penA XXXIV in the region targeted by the assay.

Conclusion

The mosaic penA XXXIV assay demonstrated 97% sensitivity and 100% specificity in predicting alert ESCs MIC values among clinical isolates tested, and was successfully multiplexed with gyrA assay. Clinical utility of this assay may be limited due to false negativity in isolates with non-XXXIV mosaic types, but it could serve as a useful surveillance tool for XXXIV mosaic.

Disclosure

R. Humphries, Roche: Consultant, Consulting fee
β-d-Glucan Testing Is Overused in Patients Without Solid Organ/Stem Cell Transplant or Hematologic Malignancies
Authors: Markou Theodore , Fabre Valeria , Mehta Seema , Shoham Shmuel , Cosgrove Sara E
Published: October 2017

Background

The β-d-glucan (BDG) assay aids in diagnosis of some invasive fungal infections (IFI) in at-risk patients. Due to an increase in the number of BDG tests ordered at Johns Hopkins Hospital in patients not at high risk for IFI, we evaluated the appropriateness of testing and conducted a survey to understand providers’ knowledge about the test.

Methods

From December 2015 to July 2016, we identified inpatients >17 years with at least one BDG test. We did not evaluate patients with solid organ/stem cell transplant or hematologic malignancies as they generally have indications for BDG testing. Using a standard data collection form, one infectious disease (ID) physician reviewed all test for appropriateness; 20% of cases were reviewed by an additional ID physician. Students, housestaff and allied staff from departments of medicine and surgery were surveyed regarding their knowledge of BDG test characteristics including indications and causes of false-positive results.

Results

355 patients with at least one BDG were included. 33% (n = 116) had a risk factor for IFI (e.g., AIDS, immunosuppressing medication, malignancy, total parenteral nutrition, and prolonged ICU stay) although only 13% (n = 48) of these had proved or possible IFI. 49% (n = 173) had no indication for testing. Of these, 4% (n = 8) had inappropriate antifungals started based on BDG results. Being at an intensive care unit or having cirrhosis was associated with inappropriate BDG use (P = 0.03). Most of the 47 clinicians surveyed recognized the utility of BDG in the diagnosis of candidiasis (63%) and Aspergillosis (78%) but only 49% recognized its utility in diagnosis of Pneumocystis. Fifty-two percent identified its lack of utility for diagnosis of Cryptococcus infection but only 44% recognized lack of utility for diagnosing Zygomycetes. The majority of those surveyed were unable to identify causes of false-positive results of the assay.

Conclusion

In patients without solid organ/stem cell transplant or hematologic malignancies, clinicians ordered the BDG assay in the absence of clinical risk or evidence of IFI in almost 50% of patients. Survey results suggest an incomplete understanding of organisms associated with positive BDG tests. Clinicians must be educated about the correct patient population in which a new test should be used.

Disclosures

All authors: No reported disclosures.
Risk Factors Predicting Candida glabrata Bloodstream Infection
Authors: O’Halloran Jane , Kronen Ryan , Lin Charlotte , Hsueh Kevin , Powderly William , Spec Andrej
Published: October 2017

Background

Increased incidence of Candida glabrata (CG) infection is a growing concern in recent years due to the higher rates of fluconazole resistance associated with C. glabrata . This study aimed to create a risk predictive model for C. glabrata in patients with culture-positive candidemia.

Methods

Demographic data, risk factors, laboratory parameters, and outcomes were retrospectively collected on all cases of candidemia occurring at a large tertiary referral hospital between January 2002 and January 2015. Between-group differences were compared using 2 square tests. A risk predictive model was built using multivariate logistic regression.

Results

Of 1,913 subjects with candidemia, 398 (21%) had C. glabrata isolated. Those with C. glabrata were older (mean [SD] 61 [23] vs. 58 [23] years; P < 0.001) and more often female (231 (58%) vs. 681 (45%); P < 0.001). On univariate analysis, age (OR 1.01 [95% CI 1.01,1.02]), gender (0.6 [0.5, 0.7]), history of rectal cancer (2.00 [1.2, 3.5]), other GI malignancy (3.0 [1.5, 6.2]), breast cancer (1.8 [1.1, 3.0]), enteral and parenteral feeding (1.9 [1.2, 3.2]), bowel resection (3.0 [1.4, 6.2]), temperature (0.9 [0.8, 1.0], recent fluconazole use (2.0 [1.4, 2.9]), and The presence of urinary catheter (2.3 [1.4, 3.6]), central line (1.4 [1.1, 1.7) or ventilator (2.2 [1.3, 3.8]) were all associated with C. glabrata infection (P < 0.05) and included in the multivariate modeling. Age, gender, history of rectal malignancy, other GI malignancies, use of enteral or parenteral feeding and recent fluconazole use remained significant (effect size 1.2 [95% CI 1.1, 1.3]; 1.8 [1.4, 2.3]; 2.0 [1.1, 3.6]; 3.0 [1.3, 6.9]; 1.9 [1.0, 3.3]; 2.0 [1.3, 3.0], respectively). The final model had a c-statistic of 0.66 [95% CI 0.63–0.69]). Ninety-day mortality in the C. glabrata group was not significantly different from the non-C. glabrata group (40% (158/398) vs. 42.5% (644/1515).

Conclusion

Underlying bowel pathology was more commonly associated with C. glabrata candidemia than with other candida species. Further exploration of the direct association between C. glabrata and GI malignancy and indirect effects of prior surgery or antifungal use on risk of C. glabrata candidemia are required. Interestingly, mortality did not differ between groups with glabrata and non-glabrata candida blood stream infections. This may reflect increasing empiric use of echinocandin therapy.

Disclosures

A. Spec, Astellas Pharma US, Inc.: Grant Investigator, Research grant
Real-World Experience of Voriconazole Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Single-Center Study
Authors: Chan Shuk-Ying , Neofytos Dionysios , Hughes Rachel M , Huang Yao-Ting , Perales Miguel-Angel , Papanicolaou Genovefa
Published: October 2017

Background

High rates of discontinuation of voriconazole (VCZ) antifungal prophylaxis (AFP) due to toxicities have been reported from single centers in allogeneic hematopoietic (allo-HCT) recipients. We sought to describe (i) adherence to AFP guidelines and (ii) reasons for premature VCZ discontinuation (D/C).

Methods

Retrospective review of 215 adult allo-HCT recipients from September 1, 2014–December 31, 2015 at our center. Per standards of care (SOC), patients received micafungin from Day 2 post-allo-HCT, then switched to VCZ by D7 unless contraindicated, and remained on AFP until cessation of immunosuppression or D100 for high-risk patients. AFP modification, D/C and treatment emergent adverse events (TEAE) regardless of causality were captured through D100. Standard definitions were used for invasive fungal infections (IFI).

Results

Of 215 patients, 42 had contraindications to VCZ at baseline. Of 173 patients included in the analysis, 65 (37.6%) received ex vivo T-cell depleted (TCD) peripheral blood (PB), 15% cord and 47.4% conventional PB or marrow allografts. All TCD recipients received myeloablative conditioning (MA) and all cord recipients received reduced intensity conditioning (RIC). For conventional transplant, 65.9 and 26.8% of the patients received RIC and MA, respectively. One hundred and sixty-eight (97%) patients had normal liver function tests (LFT) at VCZ initiation. One hundred and twenty-nine (74.6%) patients started VCZ by D7 and 95% started by D15. Median duration of VCZ AFP was 68D (IQR 22–91). Abnormal LFTs was the most frequently encountered TEAE (42/58, 72%), followed by neurologic/visual TEAE (11/58, 19%) leading to VCZ D/C. Median time to VCZ D/C due to neurologic/visual TEAE (4D, IQR 4–9) was significantly shorter than abnormal LFTs (25D, IQR 16–42) (P < 0.05). Eight (5%) breakthrough proven/probable IFIs were observed by D180, without significant difference based on transplant types or AFP duration. Duration and reasons for VCZ D/C were shown in Table 1 by HCT type.

Conclusion

75% of the patients started VCZ per SOC and 95% by D15. Most TEAE leading to VCZ D/C were abnormal LFTs in all HCT types, and most commonly in cord HCT. 3) Neurologic/visual TEAE were similar across types. Rates of IFI were 3–4% in CONV and TCD and 12% in UCB.

Disclosures

Y. T. Huang, Merck & Co.: Grant Investigator, Research grant. M. A. Perales, Merck: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. Astella: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. G. Papanicolaou, Astellas Pharma: Consultant and Grant Investigator, Consulting fee, Research grant and Research support. Merck &Co: DSC member and Investigator, Consulting fee, Research grant and Research support
Invasive Mold Infections (IMI) among Liver Transplant Recipients (LTR): Is It Time to Reconsider the Risk Factors that Determine Antifungal Prophylaxis?
Authors: Neyra Karyna , Brizendine Kyle
Published: October 2017

Background

IMI have high mortality among LTR. Prevention is critical. Data supporting guideline-recommended three-tiered approach to antifungal prophylaxis based on risk for IMI are lacking.

Methods

Retrospective study of 534 adult LTR at the Cleveland Clinic (CCF) August 2010–December 2014. We analyzed the association between IMI and risk factors: retransplantation, hemodialysis, reoperation, and fulminant hepatic failure. Model of end-stage liver disease (MELD) was evaluated as novel risk factor. We compared the incidence of IMI among three subgroups: no antifungal prophylaxis, prophylaxis against yeast alone, and prophylaxis against yeast and mold.

Results

Mean age was 56 ± 11 years. 68% were male (n = 364). The most common underlying diseases were hepatitis C virus (32%), hepatocellular carcinoma (28%), alcoholic cirrhosis (19%), and nonalcoholic steatohepatitis (19%). The overall incidence of IMI was 0.9% (n = 5). The incidence of IMI among LTR with (n = 128) and without (n = 406) risk factors was 0.78 and 0.98%, respectively (see Figure). Table 1 details the risk factors and outcomes by subgroups. Only one patient with IMI had a risk factor for mold (reoperation). The other four had none. Incidence of IMI among LTR who did not receive antifungal prophylaxis was 1 and 0% in those who received yeast or mold prophylaxis. There was no association between MELD and IMI.

Conclusion

Risk factors and MELD did not predict IMI. Because risks are used to recommend mold-active prophylaxis, antifungal agent overuse may be a concern. Additional studies are needed to reconsider risk factors so that transplant providers may target antifungal agents appropriately, practice antifungal stewardship and improve outcomes.

Disclosures

All authors: No reported disclosures.
Antifungal Resistance Patterns in Molds Isolated from Wounds of Combat-Related Trauma Patients
Authors: Keaton Nicholas , Mende Katrin , Beckius Miriam , Farmer Aaron , Rizzo Julie , Ganesan Anuradha , Murray Clinton K , Tribble David R , Blyth Dana M
Published: October 2017

Background

An outbreak of trauma-related invasive fungal infections (IFI) occurred in US service members injured in Afghanistan. Empiric treatment included voriconazole (VORI) and amphotericin (AMB) and aggressive surgical debridement. Antifungal susceptibilities (AS) and relation to outcomes are yet to be described.

Methods

Between 2009 and 2013, military trauma patients with initial unique and serial (>3 days after initial isolation) molds isolated from wounds and admitted to Brooke Army Medical Center as part of the Trauma Infectious Disease Outcomes Study were assessed. The AS to AMB, VORI, posaconazole (POSA), isavuconazole (ISA), itraconazole, and caspofungin were determined by broth microdilution with CLSI breakpoint interpretations for Aspergillus spp. and mucormycetes (MM).

Results

Included are 18 patients with 28 initial mold isolates with 72% of IFI diagnosed via histopathology. All patients were male with a median of eight operations. There was a median of 11 days post-injury to mold culture. Initial isolates were five Aspergillus spp., three MM, three Fusarium spp., and combinations of three Aspergillus and MM, two Aspergillus and Fusarium, one Aspergillus and Bipolaris, one MM and Fusarium. A. flavus (AFL) and A. fumigatus (AFU) were all susceptible to AMB and POSA and 25% of AFL were intermediate to VORI. Four A. terreus (AT) isolates had MICs to AMB of 0.25, 1, 2, and 4, and were susceptible to VORI. ISA MIC50 and 90 were one and two for Aspergillus spp. Fusarium spp. MICs were >16 for VORI, POSA, and ISA, with AMB MIC50/90 of two and three. Among MM isolates, 86% were susceptible to AMB and 29% to POSA, and ISA MIC50 and MIC90 were 8 and >16. Five patients had serial isolates. One with serial AFL and AFU received no antifungal therapy, one with AT was treated with VORI, AMB, and POSA, and one with AFL was treated with AMB with no new resistance. The patient with serial MM was treated with AMB and VORI and remained resistant to POSA, but susceptible to AMB. Serial A. elegans acquired new POSA and AMB resistance and ISA MIC increased from 4 to 16 after AMB and VORI exposure.

Conclusion

Antifungal exposure to AMB and VORI was not associated with new resistance within Aspergillus spp., but 50% of MM exposed to this combination developed POSA and AMB resistance. Despite resistance of Fusarium, it was not isolated on subsequent debridements.

Disclosures

All authors: No reported disclosures.