bluuebunny/crossref_metadata_2025 huggingface dataset:
1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections
Authors: Yong Joy , Lip Chew Ka , Tambyah Paul
Published: October 2019

Background

Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro susceptibility and is being increasingly employed in treatment regimens for MabsC infections. We performed a drug-use-evaluation of clofazimine in the treatment of MabsC infections.

Methods

A retrospective review was performed for all patients with MabsC infections treated with clofazimine-containing regimens from January 2014 to June 2017.

Results

Twenty-nine patients were included. Twelve patients had pulmonary MabsC infections and seventeen had extrapulmonary infections. All isolates had clofazimine minimum-inhibitory-concentration of ≤0.5 mg/L as tested by broth microdilution. Clofazimine was prescribed at initiation of therapy in 31.0% (9/29), as a companion drug during maintenance therapy after initial intravenous therapy in 44.8% (13/29) and as part of salvage therapy due to disease progression or drug intolerance in 24.1% (7/29) of patients. Dosing of clofazimine for the pediatric patients was prescribed at 1–2 mg/kg/day while the adult patients received a range of 50–200 mg/day. Clofazimine was given for a median duration of 148.5 days (range: 14–1212) and most commonly in combination with clarithromycin (82.8%), amikacin (58.6%), and cefoxitin (24.1%). Twelve patients had documented adverse reactions attributable to clofazimine: skin hyperpigmentation (66.7%), abnormal liver function tests (16.7%), and gastrointestinal disturbance (16.7%). Table 1 describes the patients who had clofazimine ceased due to an adverse effect. Nine patients with pulmonary MabsC infections and 16 with extrapulmonary MabsC infections had documented improvement in symptoms.

Conclusion

Clofazimine as a companion drug in the treatment of MabsC infections was reasonably tolerated over a prolonged period of time. Its availability as an oral active agent makes it an attractive alternative to IV companion drugs and potentially improves compliance to the protracted treatment courses for patients with MabsC infections.

Disclosures

All authors: No reported disclosures.
1390. A Novel Application of the Interferon-Gamma Release Assay (IGRA) Among End-Stage Heart Failure Patients Awaiting Heart Transplantation
Authors: Tsai Ming-Jui , Cheng Aristine , Sun Hsin-Yun , Chen Yih-Sharng , Chou Nai-Kuan , Wang Sheoi-Shen , Chen Yee-Chun , Chang Shan-Chwen
Published: October 2019

Background

The optimal approach to assay the immune status in heart failure is challenging because of the inherent complexity of chronic inflammation. Interferon-gamma release assays (IGRAs) measure an aspect of cell-mediated immunity encompassing both the innate and adaptive immunity. In this study, we evaluated the utility of a commercial IGRA for predicting mortality and infectious complications among heart transplant candidates.

Methods

This prospective cohort study was conducted between August 1, 2014 and January 31, 2019 at a medical center in Taiwan. All heart transplant candidates received an IGRA (QuantiFERON®-TB Gold In-Tube, QFT-GIT) at baseline as part of the initiative to screen for latent tuberculosis. Impaired cell-mediated immunity was defined as the release of <1 IU/mL of interferon-γ (IFN-γ) in response to the common mitogen in the positive control tube.The patients were then followed until death or January 31, 2019.

Results

A total of 102 patients were enrolled; of whom, 23 (22.5%) had impaired cell-mediated immunity at baseline. During the study period with a median follow-up of 1.90 years (IQR 1.17–3.56), 23 (22.5%) patients died and 45 (44.1%) patients developed an infectious complication. Overall mortality was significantly greater among those with impaired cell-mediated immunity [39.1% (9/23) vs. 17.7% (14/79), P = 0.031]. A trend toward higher rates of infection was observed among impaired cell-mediated immunity group [60.9% (14/23) vs. 39.2% (31/79), P = 0.066]. The most common cause of death was infection (56.5%). No patient developed active tuberculosis during the study and the most common infection was bacteremia (35.6%). In the age-adjusted multivariate analysis, impaired cell-mediated immunity was an independent predictor of mortality (HR 2.87, CI 1.23–6.68, P = 0.014) and subsequent infectious event (HR 3.00, CI 1.56–5.76, P = 0.001).

Conclusion

An interferon-γ release assay utilizing the positive control tube of the QuantiFERON®-TB Gold In-Tube kit was predictive of overall mortality and infections among patients with advanced heart failure awaiting heart transplantation.

Disclosures

All authors: No reported disclosures.
1404. The FilmArray Meningitis/Encephalitis (FA ME) May Be of Higher Yield in the Immunocompromised Patient Population
Authors: Mehta Nirja , Jacob Jesse T , Dean Christina , Wiley Zanthia , Burd Eileen , Kraft Colleen
Published: October 2019

Background

The FilmArray® Meningitis/Encephalitis (FA ME) panel is a PCR-based assay that rapidly detects 14 pathogens directly from CSF specimens. After the introduction of this assay at our institution, there was a steady increase in requests for use; however, the positivity rate remained stable. We sought to understand the characteristics of the patients most likely to have a positive FA ME panel, with particular interest in the immune status of each patient.

Methods

A retrospective chart review was conducted on 124 patients with suspected infectious meningitis/encephalitis at a large academic tertiary referral center who received FA ME testing between October 2016 and November 2018. Patients were considered immunocompromised if they had received chemotherapy, were solid-organ transplant recipients, or were diagnosed with HIV, autoimmune diseases on immunosuppressants, uncontrolled diabetes, cirrhosis, or hematologic malignancy. Clinical CNS infection was determined using chart review based on culture, serologic, or molecular data.

Results

60 (48%) patients were immunocompromised and 64 (52%) patients were immunocompetent. Clinical CNS infection occurred in ~25% of immunocompetent (17, 26%) and immunocompromised (17, 28%) patients. However, only 6 immunocompetent patients were found to have a positive FA ME; this accounts for only 35% of the total number of positive FA ME assays during this study period (P = 0.08). Notably, 4 out of 6 patients with cryptococcal meningitis had false-negative results on the FA ME.

Conclusion

In spite of the relatively small sample size, there was a trend toward significance in the accurate yield of the FA ME panel in the immunocompromised population compared with the immunocompetent. Our immunocompromised patients appear to be more likely to have an infection which is tested for on the panel. The rates of confirmed CNS infections in both populations were very similar, indicating that immunocompromised patients may benefit more from use of this assay. In our study, immunocompetent patients were more likely to have West Nile infection, for example, which is not on the panel. Additionally, had cryptococcal meningitis been accurately diagnosed by the FA ME, an even greater number of immunocompromised patients would have had a positive FA ME.

Disclosures

All authors: No reported disclosures.
1411. Differentiation of Fungal Abscess of Brain From Brain Glioblastoma by MRI Scan ADC Value
Authors: Aziz Kashif , Nawaz Atif
Published: October 2019

Background

Differentiation of Brain fungal abscess from brain glioblastoma is very important. Treatment strategies are different in both cases. Glioblastoma needs different surgical planning as compared with abscess. We hypothesized that preoperative MRI brain will help in differentiation.

Methods

A retrospective study was carried out at Aga Khan University Hospital Karachi. Data from 2007 to 2017 was retrieved from Medical records using ICD-9 coding. 90 patients (47 males and 43 females; age range 10–70 years) with aggressive grade IV brain lesion and fungal abscess was selected and their preoperative MRI data were retrieved. The apparent diffusion coefficient (ADC) maps were reconstructed from diffusion-weighted imaging DWI data. The mean ADC value and standard deviation of glioblastoma and fungal abscesses were calculated. Postoperative biopsy results were used as gold standard.The analysis of data was done to test statistically significant differences between glioblastoma and fungal brain abscess. Receiver operating characteristic (ROC) curve was used to determine the cut-off point with highest accuracy that was used to differentiate malignancy from infection. The statistical analysis of data was done using SPSS® v. 19.

Results

The mean (±standard deviation) ADC value of fungal brain abscess (826.040 ± 94.97 × 0.001 mm2/sec) was significantly lower than that of glioblastoma (1,462.800 ± 163.66 × 0.001 mm2/sec). When an ADC value of 1,200 × 0.001 mm2/s used as a cutoff value for differentiating fungal abscess from glioblastoma the best result was obtained with an accuracy of 85%, sensitivity of 81%, specificity of 88%, negative predictive value of 80%, and positive predictive value of 90%.

Conclusion

ADC value is a noninvasive promising imaging parameter that can be used for differentiation of fungal brain abscess and glioblastoma on preoperative scan. The cut-off value with best accuracy in our study was 1,200 × 0.001 mm2/s.

Disclosures

All authors: No reported disclosures.
1414. Time-to-Completed-Imaging, Survival, and Function in Patients with Spinal Epidural Abscess: Description of a Series of 34 Patients, 2015–2018
Authors: King Caroline , Fisher Cameron , Brown Patrick , Priest Kelsey , Tanski Mary , Sullivan Peter
Published: October 2019

Background

Spinal epidural abscess (SEA) is a rare and life-threatening infection with increased incidence over the past two decades. Delays in diagnosis cause significant morbidity and mortality among patients. The objective of this study was to describe average time-to-imaging and frequencies of intervention, risk factors, and outcomes among patients with SEA presenting to an emergency department at a single academic health center in Portland, Oregon.

Methods

This retrospective cohort study reviewed data from patients with no prior history of SEAs at a single hospital from October 1, 2015 to April 1, 2018. We report measures of central tendency and frequencies of collected information.

Results

Of the 34 patients included, seven (20%) died or were discharged with plegia during the study period. Four others (11.8%) had motor weakness, and four (11.8%) patients had new bowel or bladder dysfunction at discharge. Those who died or were discharged with plegia (n = 7) had shorter mean time-to-imaging order (20.8 hours vs. 29.2 hours). Patients with a history of intravenous drug use had a longer mean time-to-imaging order (30.2 hours vs. 23.7 hours) vs. those without a history of intravenous drug use. Furthermore, only three (42.9%) of the seven patients who died or acquired plegia presented with the three symptom classic triad of SEA: (1) fever; (2) abnormal neurologic examination or symptoms; and (3) neck or back pain.

Conclusion

SEA is a potentially deadly infection requiring prompt identification and treatment. This research provides baseline data for potential quality improvement work at the study site. Future research should evaluate multi-center approaches for identifying and intervening to treat SEA, particularly among patients with a history of intravenous drug use.

Disclosures

All authors: No reported disclosures.
1418. Clinical Characteristics of Vertebral Osteomyelitis in Cancer Patients
Authors: Fukushima Kazuaki , Horiuchi Masao , Sekiya Noritaka
Published: October 2019

Background

Vertebral osteomyelitis (VOM) is an infection of vertebrae or intervertebral disc and associated with high mortality, decreased functional status, prolonged antibiotic use and recurrent infection. Although most of the patients with VOM often embody immunodeficiency or other comorbidities, characteristics of VOM in cancer patients remain to be fully elucidated. The aim of this study was to describe clinical profile, underlying disease, lesion site, pathogen, comorbidities, treatment, and outcome in patients with cancer.

Methods

This study was a retrospective observational study in a tertiary care cancer hospital with 801 beds. All patients with VOM were diagnosed by computed tomography or magnetic resonance imaging from July 2004 to March 2019. Culture-confirmed VOM was defined when causative pathogens were identified from the lesion site including vertebra, intervertebral disc, paravertebral or epidural abscess or when the result of blood culture was positive with compatible clinical symptoms. Data including patient characteristics, underlying diseases, lesion sites, type of infection, entry site of infection, results of bacterial culture, treatment, and outcome were collected by electronic medical records. We analyzed data of patients with culture-confirmed VOM between patients with cancer (C-VOM) and patients without cancer (NC-VOM). Death or re-treatment was the primary outcome. Statistical analysis was performed by STATA Version 15.

Results

Total number of patients diagnosed with VOM was 101, of which culture-confirmed VOM was 61 (C-VOM: 30 and NC-VOM: 31). Age, lesion sites, pathogen, or comorbidities were not significantly different between two groups (table). On the other hand, the rate of contiguous infection in C-VOM was significantly higher than NC-VOM (20.0 % vs. 0.0 %; P = 0.01). Univariate cox proportional hazard model revealed that cancer was risk of death or re-treatment (HR:3.14, 95% CI:1.07–9.24).

Conclusion

Poor prognosis and contiguous infection from adjacent infection sites should be concerned cancer patients with culture-confirmed VOM.

Disclosures

All authors: No reported disclosures.
1419. A Rare Case of Clostridium beijerinckii Traumatic Osteomyelitis
Authors: Doktor Katherine L , Heffernan Kelsey , Drames Danielle , Byrne Dana D
Published: October 2019

Background

We present a case of Clostridium beijerinckii osteomyelitis in the presence of retained foreign bodies not seen on MRI.

Methods

A 45-year-old female with type 2 diabetes sustained multiple open right leg injuries, grossly contaminated with gravel, after a motor vehicle collision. She underwent external fixation (ex-fix) and 5 irrigations and debridements (I&D) initially. Polymicrobial intraoperative cultures (Cx) were treated with vancomycin and ertapenem for 6 weeks. One month post-antibiotic completion, pain, and swelling developed in ankle; contrast MRI revealed avascular necrosis and osteomyelitis (OM) of talus. Cx from repeat I&D grew same organisms; meropenem was recommended for 6 weeks. During meropenem week 6, pain was minimal and wound was closed. During attempt to implant hardware, pus was seen around peroneal tendon. Cx grew Clostridium species and Bacteroides from tibia, calcaneus, talus, and peroneal tendon sheath; meropenem was continued. Pain worsened 3 weeks later; I&D revealed pus in lateral ankle. To better access the medial ankle, a longitudinal incision was made along posterior tibial tendon, perpendicular to prior surgical incision. Immediate purulence, grass blades, and rocks were seen. Brucella agar had a rare gray colony at 48 hours and was subbed to blood and Brucella agar; it grew on Brucella agar with aero tolerance test. Gram stain showed Gram-positive rods with subterminal spores. Rapid ANA panel identified isolate as Clostridium beijerinckii (Cb) with > 99.9% probability and bioscore 1/24.

Results

Cb is a strict anaerobic gram-positive rod with oval subterminal spores. Found in soil and water, its main use is industrial solvent production. Infection by Cb is rare; only 2 cases of OM, 1 traumatic endophthalmitis, and 1 mitral valve endocarditis have been reported. While uncommon, Clostridial osteomyelitis is associated with contaminated open traumatic injuries. It can be difficult to eradicate, despite aggressive surgical intervention and appropriate antibiotics.

Conclusion

This is the third case of Cb OM described. Anaerobic cultures should be collected during I&D of open traumatic wounds. If infection persists, careful intraoperative evaluation of wound for residual foreign bodies, even if not seen radiologically, should be performed.

Disclosures

All authors: No reported disclosures.
1475. Understanding Prescribing Practices for Uncomplicated Urinary Tract Infections (UTIs) in the Primary Care Setting: A Pilot Study
Authors: Pinkerton Mark , Bongu Jahnavi , James Aimee , Durkin Michael
Published: October 2019

Background

Uncomplicated urinary tract infections (UTIs) should be treated empirically with a short course of narrow-spectrum antibiotics. However, many clinicians order unnecessary tests and treat with long courses of antibiotics. The objective of this study was to understand how internists clinically approach UTIs.

Methods

We conducted semi-structured qualitative interviews of community primary care providers (n = 15) and internal medicine residents (n = 15) in St. Louis, Missouri from 2018 to 2019 to explore why clinical practices deviate from evidence-based guidelines. Interviews were transcribed, de-identified, and coded by two independent researchers using NVivo qualitative software. A Likert scale was used to evaluate preferences for possible interventions.

Results

Several common themes emerged. Both providers and residents ordered urine tests to “confirm” presence of urinary tract infections. Antibiotic prescriptions were often based on historical practice and anecdotal experience. Providers were more comfortable treating over the phone than residents and tended to prescribe longer courses of antibiotics. Both providers and residents voiced frustrations with guidelines being difficult to easily incorporate due to length and extraneous information. Preferences for receiving and incorporating guidelines into practice varied. Both groups felt benchmarking would improve prescribing practices, but had reservations about implementation. Pragmatic clinical decision support tools were favored by providers, with residents preferring order sets and attendings preferring nurse triage algorithms.

Conclusion

Misconceptions regarding urinary tract infection management were common among residents and community primary care providers. Multifaceted interventions that include provider education, synthesis of guidelines, and pragmatic clinical decision support tools are needed to improve antibiotic prescribing and diagnostic testing; optimal interventions to improve UTI management may vary based on provider training level.

Disclosures

All authors: No reported disclosures.
1483. Comparison of Outcomes in Urinary Tract Infections Caused by SPICE Organisms Treated with Non-Carbapenem-β-lactams vs. Non-β-lactams Agents
Authors: Sapozhnikov Julia , Huang Angela , Powell Kelsey , Gibble Allison
Published: October 2019

Background

The “SPICE organisms” intrinsically produce low levels of a chromosomally encoded β-lactamase enzyme, AmpC. When SPICE organisms are exposed to certain antimicrobial agents, they can select for de-repressed mutants and induce the AmpC gene. No study to date has determined the optimal treatment of lower inoculum infections such as urinary tract infections (UTIs) caused by SPICE organisms.

Methods

This study is a single-center, retrospective observational review of adult hospitalized patients with a UTI caused by a SPICE organism from November 2012 to November 2015. The objective of this study was to compare outcomes amongst patients with UTIs caused by select SPICE organisms treated with drugs susceptible to AmpC hydrolysis (penicillins, cephalosporins except cefepime, and monobactams) vs. drugs stable against AmpC (carbapenems, cefepime, and non-β-lactam agents). The primary outcome was clinical response, defined as resolution of signs and symptoms of UTI without requiring escalation of antimicrobial therapy after 48 hours of therapy initiation. Secondary outcomes include 30-day infection-related readmission, 30-day infection recurrence rate, 30-day all-cause mortality, and length of hospital stay. Patients with resistance to ceftriaxone were reviewed for β-lactam exposure (≥7 days) within the last month.

Results

One-hundred 56 patients were identified. Clinical response, 30-day infection-related readmission, 30-day infection recurrence, 30-day mortality rates, and median length of hospital stay were similar between the AmpC stable and AmpC susceptible groups (Table 1). Notably, 39.1% of patients with ceftriaxone resistance reported had recent β-lactam exposure vs. only 11.6% of patients without ceftriaxone resistance (P = 0.0028).

Conclusion

Based our data, there does not appear to be a difference in clinical response, 30-day-related readmission, 30-day infection recurrence, 30-day all-cause mortality rates, or length of stay in patients with UTIs treated with AmpC stable and AmpC susceptible agents. AmpC induction can be seen with at least 7 days of β-lactam use in the past 30 days as demonstrated by more frequent use of recent β-lactam agents in those with ceftriaxone resistance detected.

Disclosures

All authors: No reported disclosures.
1522. Clinical and Molecular Epidemiology of Invasive Haemophilus influenzae Serotype a Infections in Utah Children
Authors: Crandall Hillary , Christiansen Jennifer E , Varghese Alyssa , Russon Adam K , Korgenski Kent , Dickey Mandy , Killpack Jarrett , Knackstedt Elizabeth , Daly Judy , Ampofo Krow , Pavia Andrew , Bonkowsky Anne
Published: October 2019

Background

Following widespread use of the Haemophilus influenzaeserotype b (Hib) vaccine,H. influenzae serotype a (Hia) has emerged as an important pathogen in children. Rates of Hia disease are particularly high in Utah. We describe the clinical features and molecular epidemiology of invasive Hia disease in children in Utah over 11 years.

Methods

Cases of invasive Hia disease in children less than 18 years were identified through electronic clinical and microbiology records. Demographic data and clinical outcomes were abstracted from the medical record for all cases. Available Hia isolates were collected for molecular analysis. Isolates were genotyped by multi-locus sequence typing (MLST) and clonal division was determined using sodC PCR. Presence or absence of the putative virulence-associated IS1016-bexA duplication-deletion was evaluated.

Results

We identified 51 children with invasive Hia between 2007 and 2017. Median age was 11.3 months. The average annual incidence was 1.7 cases per 100,000 children aged <5 years (95% CI 1.2–2.2). Incidence was highest among children less than one year of age (4.8/100,000; 95% CI 3.1–6.9). Incidence rates were similar by race and ethnicity, although the confidence intervals were wide. The annual number of cases was similar over the 11-year study period (figure). The most common clinical manifestation was meningitis (54%; half had intracranial complications, 25% suffered hearing loss), followed by pneumonia (14%), and arthritis (14%). Twenty-two children (44%) required ICU care and one child died. Twenty-eight isolates (56%) were available for molecular analysis. ST62, clonal division II isolates caused 75% (21/28) of disease. No isolates contained the virulence-associated IS1016-bexA duplication-deletion.

Conclusion

Hia is an important cause of severe invasive bacterial infection in Utah. Molecular analyses revealed that a majority of infections were caused by ST62 isolates, a clonal division II Hia type lacking the IS1016-bexA duplication-deletion. Hia ST62 has not been commonly reported in other settings, suggesting a unique molecular epidemiology in our population.

Disclosures

All authors: No reported disclosures.
1548. Characterizing Cefepime Neurotoxicity: Experience from a Tertiary Care Center Performing β-lactam Therapeutic Drug Monitoring
Authors: Nys Cara , Hurst Natalie , Liu Jiajun , Cherabuddi Kartikeya , Iovine Nicole M , Scheetz Marc H , Rhodes Nathaniel J , Klinker Kenneth , Veena Venugopalan
Published: October 2019

Background

Based on prior studies, elderly patients and those with renal dysfunction are prone to cefepime (CFP) toxicity. The toxicokinetics and toxicodynamics for CFP are not well established. Lamoth et al. reported a 50% probability of CFP neurotoxicity at a serum trough concentration of ≥22 mg/L, whereas Huwyler et al. observed CFP neurotoxicity when concentrations exceeded 35 mg/L. The objectives of this study were to quantify the incidence of CFP neurotoxicity and to assess the association between CFP concentrations and neurotoxicity.

Methods

We conducted a retrospective review between March 2016 and May 2018, of adult patients with serum CFP trough concentrations ≥25 mg/L. To be considered a CFP neurotoxicity case, patients were required to fulfill at least two of the NCI criteria for neurological toxicity such as, presence of new-onset confusion, delirium, or drowsiness. Following this, cases were classified as (1) high likelihood of toxicity (HLT) if they either had a neurology consult or EEG findings consistent with CFP toxicity and if their symptoms improved after discontinuation of CFP, (2) possible toxicity (PT) if neurology consult or EEG was absent or if we were unable to assess improvement after CFP was discontinued, or (3) nontoxicity (NT). Cases were independently reviewed by an ID pharmacist and physician. Additional data such as comorbidities, renal function, and use of anti-epileptics were collected.

Results

One hundred and forty-two patients were included in the analysis. Neurotoxicity (HLT+PT) related to CFP occurred in 18/142 (13%) patients; 67% (12/18) were considered HLT. The median age in the HLT cohort was 68 years (interquartile range [IQR], 57–74), with toxicity occurring a median of 6 days (IQR, 5–8) after starting CFP. At the time of neurotoxicity, HLT patients had diminished renal function with a median SCr of 1.6 mg/dL (IQR, 1.2–2.4) and a corresponding CrCl of 35.8 mL/minute (IQR, 19.2–50.9). The median CFP trough concentration in the HLT patients was 62 mg/L (IQR, 50–73) vs. 70mg/L (IQR, 41–115) in the PT and 42 mg/L (IQR, 31–61) in the NT groups.

Conclusion

Our data emphasize the need for careful dosing in older patients with renal insufficiency. Interestingly, our study reveals higher cefepime troughs (~3-fold higher) associated with neurotoxicity than previously reported.

Disclosures

All authors: No reported disclosures.
1569. A Translational Model to Assess the Impact of Polymyxin B Dose Fractionation on Kidney Injury
Authors: Liu Jiajun , Pais Gwendolyn M , Avedissian Sean N , Lee Andrew , Rhodes Nathaniel J , Hauser Alan R , Scheetz Marc H
Published: October 2019

Background

Progression of antimicrobial resistance has revived Polymyxin B (PB) use in clinical practice. Dose-dependent acute kidney injury (AKI) limits its clinical use. It is unclear whether dose fractionation of total daily dose can lessen kidney injury. We assessed the role of PB fractionation on AKI in a translational model that employs sensitive urine biomarkers qualified by the FDA.

Methods

Male Sprague–Dawley rats received 12 mg/kg/day PB subcutaneously for 3 days or equal-volume normal saline (NS). PB was administered in 3 separate fractionated daily doses: 12 mg/kg daily (QD), 6 mg/kg twice daily (BID), and 4 mg/kg thrice daily (TID). Staggered blood sampling was done on days 1 to 4 and 24 hour urine was collected at baseline, on days 1, 2, and 3. Plasma creatinine (Cr) was quantified using LCMS/MS, and 24 hour urinary biomarkers (KIM1, OPN, CLN, calbindin, GSTα, IP-10, TIMP-1, and VEGF) were assayed with MILLIPLEX Rat Kidney Toxicity Magnetic Bead Panel. Mixed-effects models were used.

Results

A total of 32 rats contributed to the study data. Mean Cr were constant across groups over time (Figure 1, P = 0.18). For NS group, all biomarkers remained at baseline throughout study. Significant differences were seen for fractionation schemes for KIM1 (P = 0.02), CLN (P = 0.03), IP-10 (0.007) and TIMP-1 (P = 0.04). The differences for KIM1, IP-10, and TIMP-1 were driven by higher observed values in TID than those of BID as early as day 1 (P < 0.04). Furthermore, CLN was elevated for TID when compared with BID at baseline (P = 0.048). Similarly, TID group had the highest (but non-significant) elevations for IP-10 and TIMP-1 compared with QD on study days. Amongst all urine biomarkers, KIM1 in TID exhibited the most rapid rise from baseline to day 2 (Figure2, P < 0.0001).

Conclusion

In this translational model in which a single total daily dose was fractionated, sensitive urinary biomarkers indicated that TID dosing was worse than BID or QD dosing; dose fractionation of PB may lead to increased AKI. In addition, KIM1 rose rapidly as an early marker for AKI. Further efforts are needed to investigate the PK-TD relationship of PB in order to decrease AKI.

Disclosures

All authors: No reported disclosures.
1570. Association Between Vancomycin Area Under the Curve (AUC) and Nephrotoxicity
Authors: Poston-Blahnik Anna , Moenster Ryan P
Published: October 2019

Background

It is unclear whether increased vancomycin area under the curve (AUC) contributes to acute kidney injury (AKI) risk.

Methods

This retrospective cohort study was undertaken to determine whether vancomycin AUC > 550 is associated with a higher rate of AKI than an AUC < 550. Patients treated with vancomycin for at least 4 days at the St. Louis VA from 1/1/2016–9/31/2018 were included. The primary outcome was AKI (defined as an increase in serum creatinine by 0.3 mg/dL or 50% from baseline). Secondary outcomes included length of stay, readmission, or mortality in 30 days, AKI rate with concurrent antibiotics, and AKI rate with comorbidities. The AUC was calculated as daily dose (in mg) divided by vancomycin clearance. The variables of age ≥ 70, vancomycin AUC ≥ 550, creatinine clearance (CrCl) < 50 mL/minute, concomitant antibiotic administration, vancomycin treatment ≤ 7 days, and the presence of comorbidities were included in a bivariate analysis. Variables with a P-value of <0.2 were included in a multivariate logistic regression model.

Results

Two hundred patients were included in the analysis; 100 patients with an AUC ≥ 550, and 100 with an AUC < 500. Only mean vancomycin dose (1722.50 mg vs. 2361.25 mg; P < 0.05), mean AUC (465.88 vs. 696.45; P < 0.05), and peak SCr (1.22 mg/dL vs. 1.48 mg/dL; P = 0.015) were significantly different between groups; AUC < 550 vs. AUC ≥ 550, respectively. Acute kidney injury occurred in 22% (44/200) of all patients; 42% (42/100) with a calculated AUC ≥ 550 developed AKI compared with 2% (2/100) of patients with an AUC < 550 (P < 0.05). The secondary outcomes of concomitant nephrotoxic agents, length of stay, readmission at 30 days, and 30-day mortality were not significantly different between groups. Only age ≥ 70, vancomycin AUC ≥ 550, CrCl < 50 mL/minute, concomitant piperacillin–tazobactam administration, and the presence of comorbidities were included in the multivariate regression. Age ≥ 70, CrCl < 50 mL/minute, and AUC ≥ 550 [OR 49.5 (95% CI 10.1 – 242.3; P < 0.05)] were found to be independently associated with risk for developing AKI.

Conclusion

Patients with a calculated vancomycin AUC ≥ 550 were found to have a significantly higher rate of AKI compared with those with an AUC < 550.

Disclosures

All authors: No reported disclosures.
1575. Vancomycin Loading Doses and Nephrotoxicity on Medicine Teaching Services
Authors: Wagner Phillip , Arnold Jon , Sheridan Kathleen R
Published: October 2019

Background

IDSA guidelines recommend the usage of a loading dose when using vancomycin for seriously ill patients to rapidly achieve adequate trough concentrations. While the relationship between vancomycin and nephrotoxicity is the focus of many studies, and with the strength of that relationship still debated, few studies have examined the relationship between vancomycin loading doses and nephrotoxicity.

Methods

We performed a retrospective cohort study examining vancomycin dosing for internal medicine teaching services’ patients over the 2014–15 academic year at one academic medical center. We generated a list of all hospitalized patients aged 18–85 who received vancomycin and were admitted to a teaching service. Patient data were extracted from the inpatient EMR via manual chart review. Patients were excluded if their pretreatment calculated glomerular filtration rate (GFR) was less than 50 mL/minute, if they received less than three doses of vancomycin, or if their initial dose was subtherapeutic (<10 mg/kg). Nephrotoxicity was determined by 7-day acute kidney injury (AKI) rate. Patients in the loading dose (>20 mg/kg) cohort were compared with those in the standard dose cohort (10–20 mg/kg). Our primary modeling used multi-variable logistic regression with AKI as our outcome of interest.

Results

438 of the initial 804 patients were enrolled. The loading dose (n = 365, 83%) and standard dosing (n = 73, 17%) cohorts were not significantly different regarding demographics, GFR, nephrotoxic drug exposure, total vancomycin received, trough levels, or comorbidities, and were only significantly different regarding body mass index (BMI). The 7-day AKI rate was not significantly different between the two arms (6.3% in the standard dosing arm and 8.2% in the loading dose arm P = 0.6). AKI rate significantly increased in both arms in the setting of concurrent piperacillin–tazobactam and vancomycin administration (OR 2.5, P = .04). There was no association between BMI and AKI.

Conclusion

Few studies have examined the relationship between nephrotoxicity and vancomycin loading doses. The results of this study provide evidence that the use of loading doses is not significantly associated with increased 7-day AKI rate.

Disclosures

All authors: No reported disclosures.
1592. In Vitro Activity of Ceftolozane/Tazobactam (C/T) Against Enterobacteriaceae and Pseudomonas aeruginosa Circulating in Chile
Authors: Rivas Lina M , Martínez Jose R W , Spencer Maria , Porte Lorena , Silva Francisco , Cifuentes Marcela , Barraza Bélgica , Rojas Pamela , Araos Bralic Rafael , Tran Truc T , Miller William R , Arias Cesar A , García Patricia , Munita Jose
Published: October 2019

Background

The widespread dissemination of carbapenem-resistant (CR) P. aeruginosa and Enterobacteriaceae has created a major global public health crisis. C/T is a recently approved therapeutic which consists of the combination of a novel cephalosporin (ceftolozane) and tazobactam (a β-lactamase inhibitor). C/T has shown good activity against a wide range of multidrug-resistant (MDR) Gram negatives, being particularly interesting as an alternative for MDR P. aeruginosa. We aimed to determine the activity of C/T against clinical strains of Enterobacteriaceae and P. aeruginosa recovered in 4 large clinical centers from Chile.

Methods

We analyzed 434 isolates of Enterobacteriaceae (347 E. coli, 66 K. pneumoniae, 21 Enterobacter cloacae complex) and 57 P. aeruginosa collected during 2017 from 4 tertiary care institutions in Santiago, Chile. Identification was performed as per each local clinical microbiology lab. Susceptibility testing was performed by broth microdilution using customized Sensititre plates (Trek). Carba-NP was performed to screen for carbapenemase production. Susceptibilities were analyzed as per 2019 CLSI breakpoints.

Results

The MIC50/90 for C/T against Enterobacteriaceae and P. aeruginosa were 1/4 μg/mL and 2/16 μg/mL, respectively. In Enterobacteriaceae, susceptibility to C/T reached 92% in E. coli (Figure 1A), 91% in E. cloacae complex (Figure 1B) and 70% in K. pneumoniae (Figure 1C). Remarkably, C/T remained active against 58% (33/57) of CR Enterobacteriaceae (Figure 2A). Among Carba-NP-negative CR isolates (46%, 26/57), susceptibility to C/T was 54% (Figure 3 A–C). In P. aeruginosa, the overall susceptibility to C/T was 81% (Figure 1D), maintaining activity against 69% (25/36) of CR strains (Figure 2B). Importantly, susceptibility to C/T in CR P. aeruginosa isolates with a negative Carba-NP (67%, 24/36) was 83% (20/24) (Figure 3D).

Conclusion

In this multicenter study, we observed that C/T was highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa. Of note, C/T remained active against a large proportion of CR clinical strains. Moreover, the activity of C/T was particularly high against CR P. aeruginosa isolates with a negative Carba-NP.

Disclosures

All authors: No reported disclosures.
1616. Confronting Measles: The View from a New York City Health System at the Center of the Outbreak
Authors: Lighter Jennifer , Sterling Stephanie , McKinney Kelly , Medefindt Judith , Hochman Sarah , Stachel Anna , Pham Vinh , Phillips Michael S
Published: October 2019

Background

A measles outbreak was identified in NYC in October, 2018. Over 430 cases have been confirmed to date, mostly in under-vaccinated children. Due to referral patterns, our health system provided care to a large number of these patients in the ambulatory, Emergency Department and inpatient settings, placing significant pressure on Infection Prevention and Control efforts. Our response utilized the engineering, administrative, protective equipment and educational hierarchy of controls to prevent transmission to patients, visitors and staff.

Methods

Patients residing from outbreak zip codes were flagged in our electronic medical record. Screening for symptoms, measles exposure, vaccine opportunities and education were provided when patients presented for care. Enhanced controls for premature infants and immunocompromised patients were enacted. Automated emails to providers caring for patients from the outbreak area served as reminders to consider measles in differential diagnosis. As most cases of measles occurred in children, special effort was taken to prevent transmissions in pediatrics. Patient rooms on multiple inpatient floors were converted to negative pressure with respect to corridor, as admitted patients developed symptomatic (contagious) illness while hospitalized. We limited all nonimmune visitors <5 years from entering inpatient units. Patients were contacted prior to ambulatory visits, procedures, and surgery to ensure patients from outbreak zip codes were triaged appropriately. Automated alerts to Infection Control when measles testing was ordered allowed timely implementation of prevention measures and surveillance. Finally, educational materials for patients and visitors were translated into 7 languages and shared with other NYC hospitals.

Results

To date, 95 patients with suspect measles presented to our system, with 20 patients (16 pediatric and 4 adult) laboratory-confirmed cases requiring hospital admission due to measles pneumonia, hepatitis, and encephalitis. There was no evidence of transmission within the hospital and ambulatory setting to patients or staff.

Conclusion

A coordinated response involving engineering and administrative controls, PPE training and education is necessary when confronting a large urban measles outbreak.

Disclosures

All authors: No reported disclosures.
1618. Public Health at the United States/Mexico Border: Evaluation of the County of San Diego Health and Human Services Agency’s Health Screening Assessment of Asylum-Seeking Families at the San Diego Rapid Response Network Shelter
Authors: Horton Lucy E , Graves Susannah , Fischer Kathleen , Fleming-Magit Gina , Romero Camila , Thorne Christine , McDonald Eric , Murto Christine , Koenig Kristi L , Tuteur Jennifer M , Hill Linda
Published: October 2019

Background

Many families arrive at the United States–Mexico border seeking asylum. Jewish Family Service and the San Diego Rapid Response Network operate a shelter in San Diego that provides shelter, food, clothing, legal services and travel coordination for asylum-seeking families. Two local federally qualified health centers provide on-site urgent care.

Methods

In late December 2018, the County of San Diego expanded public health efforts by conducting health screenings of guests upon entry to the shelter with the goal of identifying health issues requiring urgent or emergent evaluation and preventing the spread of communicable disease. University of California San Diego Health physicians contracted by the County of San Diego Health and Human Services Agency (HHSA) nurses and ancillary staff provide daily on-site services to all shelter entrants including: health screening for diseases of public health significance, treatment and/or referral of urgent conditions, and medical clearance for shelter entry or medical isolation as needed. Official tracking of screening outcomes from January 2 to April 24, 2019 were collected using standardized surveys and analyzed for program evaluation and surveillance purposes.

Results

During that time a total of 9,124 asylum-seekers were screened, averaging 81 guests daily, identifying: 42 influenza-like illness, 645 lice, 330 scabies, 8 varicella, and 0 hepatitis A cases. Chest radiography for suspected tuberculosis was performed for 29 guests. Only one chest x-ray was abnormal. Sputum specimens for acid-fast stain (n = 3) and nucleic acid testing (n = 2) were all negative and no tuberculosis cases were diagnosed. Emergency department referrals were made for <1% of guests (n = 90) for conditions including pregnancy complications, asthma, dysentery, hemoptysis and fractures. No deaths or outbreaks of communicable disease occurred.

Conclusion

Coordination among local partner agencies resulted in early identification of communicable and acute health conditions prior to shelter entry allowing evaluation, treatment and off-site isolation, and minimizing stress on the emergency medical services system. This approach provides a successful model for health screening of asylum-seeking families arriving at the United States–Mexico border.

Disclosures

All authors: No reported disclosures.
1641. A Comparison of Human Papilloma Virus Infection Prevalence Trends Pre- and Post-HPV Vaccine Implementation
Authors: Ovie. Fueta Patrick , Greg Chido-Amajuoyi Onyema
Published: October 2019

Background

Human papilloma virus (HPV) is the most common sexually transmitted infection in the United States, with an annual incidence rate of approximately 14 million people. The HPV vaccine has been demonstrated to be highly effective in the prevention of HPV infection and HPV-associated diseases. This study aims to evaluate the impact of HPV vaccine on the prevalence of HPV infection in the United States and evaluate the trends of disease prevalence pre- and post-HPV vaccine implementation.

Methods

We conducted a secondary data analysis of the National Health and Education Survey (NHANES) for trends in HPV infection from 2003 to 2016. The analysis was grouped into a pre-HPV vaccine implementation (2003–2006) cohort including 4064 females, aged 18–59 years; and a post-HPV vaccine implementation (2007–2016) cohort which included 10718 females, aged 18–59 years. Further analysis of HPV infection prevalence, pre- and post-HPV vaccine implementation, stratified by sociodemographic characteristics were conducted.

Results

The prevalence of HPV infection prior to HPV vaccine implementation was 43.98% (95 CI 42.71%–46.58%) compared with 40.55% (95 C.I 40.55%–40.56%) in the post-HPV vaccine implementation era. Among females with HPV infections in the post-HPV vaccine implementation cohort 82.6 (95% CI 80.41%–83.42%) were unvaccinated. In both cohorts, black females had a significantly higher prevalence of HPV with a prevalence rate of 18.56% (95% CI 18.23%–20.56%) in the pre-HPV vaccine implementation cohort, and 15.61% (95% CI 14.82 – 19.4%) in the post-HPV vaccine implementation cohort. Females with less than high school education had a higher prevalence of HPV in the pre and post- HPV vaccine implementation cohorts with prevalence rates of 25.77% (95% CI 23.44%–28.72%) and 24.96% (95% CI 23.41%–25.67%), respectively.

Conclusion

The results suggest that HPV infection prevalence has declined since the implementation of HPV vaccine to US national immunization program. Our findings highlight disparities in HPV infection prevalence by race and educational status, and these patterns are in keeping with HPV-associated disease such as warts and HPV-associated cancers.

Disclosures

All authors: No reported disclosures.
1642. Comparing Viral Respiratory Infections Between Children Who Do and Do Not Attend Child Care
Authors: DeJonge Peter , Malosh Ryan , Truscon Rachel , Johnson Emileigh , Foote Sydney , Cheng Bonnie , Tiseo Katie E , Getz Amy S , Segaloff Hannah , Monto Arnold , Martin Emily T
Published: October 2019

Background

Out-of-home child care (CC) is a risk factor for viral acute respiratory infection (ARI) in young children. Little is known, however, about differences in frequencies of viral infection between CC children and those cared for exclusively at home.

Methods

Using surveillance data from the HIVE household cohort in southeast Michigan from 2014–2018 (4 seasons), we analyzed 1022 illness cases from 354 children aged 0–6 years. Age groups were dichotomized as infants (aged <2 years) and toddlers/preschoolers (aged 2–6 years). Households were prospectively enrolled and nasal respiratory swabs were collected from children upon report of acute illness symptoms. We used real-time RT–PCR to test for 18 respiratory viruses.

Results

We detected at least one virus in 855 illness cases (83% of all illnesses reported). Age at first illness onset in all four seasons was significantly younger among CC children than homecare children (P < 0.001) across all 4 years (average difference = 1.25 years). CC children <2 years had slightly lower odds of viral detection during illness (OR = 0.89, 95% CI [0.49, 1.61]) but higher odds at ages 2–6y (1.07 [0.65, 1.76]); neither was statistically significant. Neither CC nor homecare children were significantly more or less at risk for any particular pathogen—expect for rhinovirus in the <2-year group, where odds of rhinovirus infection were 58% lower (OR = 0.42) in CC children compared with homecare counterparts (95% CI, 0.21–0.83). Conversely, CC attendees under 3 more frequently had influenza, RSV, hMPV, parainfluenza, and coronavirus; however, none of these associations were significant. Odds of coinfection (> 1 virus detected) were higher among CC children, but not significant (OR = 1.4 [0.63, 2.96] and 1.2 [0.77, 1.88] in <2 year and 2–6 year age groups, respectively). Among all children <7 year, the mean number of pathogens detected was not different between CC and homecare individuals (1.20 vs. 1.23, P = 0.16).

Conclusion

As expected, results indicated that CC attendees aged 0–6y experienced illness episodes earlier in life compared with homecare children. Our analysis also indicated that, compared with children cared for at home, CC children were less at risk for rhinovirus infection when young but could potentially be at higher risk for viruses of greater clinical concern.

Disclosures

All authors: No reported disclosures.