bluuebunny/crossref_metadata_2025 huggingface dataset:
2253. Comparison of Outcomes Between Patients with and without Cystic Fibrosis Treated with Ceftolozane–Tazobactam for Pseudomonas aeruginosa Infections
Authors: Trisler Michael J , Tamma Pranita , Tamma Pranita , Avdic Edina
Published: October 2019

Background

Ceftolozane–tazobactam (C/T) was designed to have enhanced activity against P. aeruginosa and has been shown to retain activity against many isolates that are resistant to other antipseudomonal β-lactams. However, there are no data comparing outcomes in patients with and without cystic fibrosis (CF).

Methods

Retrospective, multicenter cohort study conducted at 5 hospitals that included all patients with P. aeruginosa infections who received C/T as definitive therapy between November 2016 and December 2018. The primary outcome at 90 days was a composite of mortality, recurrence, readmission, and inappropriate response at end of therapy (EOT). The secondary outcome was to describe baseline C/T susceptibility and emergence of resistance. All outcomes were adjudicated by 2 infectious diseases specialists.

Results

Thirty-five, 27 non-CF and 8 CF, patients were included. CF patients were younger, had greater baseline C/T resistance (50.0% vs. 8.3%, P = 0.02) and were more likely to receive combination therapy. The most common site of infection was pulmonary (71.4%) followed by intra-abdominal (14.3%) and osteomyelitis (5.7%). Overall, 54.3% of patients had an unsuccessful outcome with no difference between CF and non-CF patients (62.5% vs. 51.9%, P = 0.70). There was also no difference between each component of the primary outcome. All 4 CF patients with a baseline-resistant isolate had an appropriate response at EOT, while neither of the 2 non-CF patients did. The C/T MIC distribution in CF and non-CF patients was ≤ 2 μg/mL (0.0%, 64.2%), 4 μg/mL (50.0%, 25%) ≥ 8 μg/mL (50.0%, 8.4%). The median duration of C/T in CF and non-CF patients was 18.5 days (interquartile range [IQR], 14–37.5 days) and 15 days (IQR, 10–25 days). Ten, 7 non-CF and 3 CF, patients had a P. aeruginosa isolate cultured and tested for C/T susceptibility within 90 days of index culture with 80% having an MIC increase. Non-CF patients treated for > 14 days were more likely to have an MIC increase (P = 0.047). All CF patients had an MIC increase.

Conclusion

We did not observe a difference in the rate of unsuccessful outcome between CF and non-CF patients; however, our sample size was small. CF patients were more likely to be resistant to C/T at baseline. Resistance emerged frequently in both groups following exposure to C/T.

Disclosures

All authors: No reported disclosures.
2260. Clofazimine Safety and Efficacy for Treatment of Multidrug-Resistant Non-Tuberculous Mycobacteria (NTM)
Authors: Alameer Reem , Pfaeffle Herman , Heysell Scott
Published: October 2019

Background

Nontuberculous mycobacteria (NTM) are increasingly detected and challenging to cure given complex drug-resistance patterns and need to use often intolerable drug multidrug regimens over months to years of duration. As such, NTM infection can be associated with significant mortality and morbidity. Clofazimine is a repurposed drug used in the treatment of leprosy worldwide and increasingly in multidrug-resistant (MDR) tuberculosis. Some centers in the United States have incorporated clofazimine in the treatment of NTM but experience is limited and procurement restrictions have hampered its more widespread use

Methods

A prospective cohort study was performed in patients diagnosed with pulmonary or extrapulmonary NTM infection among those treated with clofazimine from a single center serving referrals from across the state of Virginia under an investigational new drug protocol. Data were collected through the center’s electronic medical record and included both pretreatment and follow-up host characteristics, radiological, microbiological and pathology data. Outcomes were assessed, radiological resolution, symptom improvement, and change in pulmonary function test (among patients with cystic fibrosis).

Results

Thirty-seven patients received clofazimine. NTM species for which the treatment was indicated were M. abscessus in 21 (58%), M. avium complex in 17 (45%) and 3 with M. chelonae. The most common companion drugs for M. abscessus included imipenem, tigecycline, linezolid or tedizolid, amikacin (IV induction followed by inhaled continuation phase) and azithromycin. For other basic patient characteristics refer to Table 1. Survival rate was 97%, while 73.5% had documented improvement in symptoms and only 2.9% had worsening of symptoms. Radiological resolution or partially improving were documented in 38% of the patients. there were no severe adverse events from clofazimine.

Conclusion

Adding clofazimine to multi-class antibiotic regimens for drug-resistant NTM treatment, including pulmonary M. abscessus disease, was well tolerated and led to clinical improvement in the majority of those treated. Randomized controlled studies are needed to determine the individual impact of clofazimine within and otherwise optimized regimen.

Disclosures

All authors: No reported disclosures.
2272. Evaluation of Clinical Features, Carbapenem Resistance and Risk Factors of Klebsiella Species: A 4-Year Retrospective Study in Turkey
Authors: Umit Zuhal , Sahbudak Bal Zumrut , Guner Gizem , Avcu Gulhadiye , Bozkurt Duygu , Kurugol Zafer , Vardar Fadil , Cilli Feriha , Ozkinay Ferda
Published: October 2019

Background

Gram-negative-resistant bacterial infections are increasing due to widespread use of antibiotics. Infections caused by Klebsiella spp. are an important part of healthcare-associated infections and cause morbidity and mortality. The aim of this study was to determine the epidemiological, clinical features, carbapenem resistance rates and risk factors of bloodstream infections of children with Klebsiella spp.

Methods

In this retropective study, medical records of 85 episodes of 75 patients caused by with Klebsiella spp. bacteriaemia who admitted to Ege University Faculty of Medicine, Pediatric Hospital in Turkey between 2014 and 2017 were evaluated. Conventional biochemical methods were performed using the automated systems of MALDİ-TOFF MS / VITEK 2 (Biomerieux, France). According to EUCAST recommendations, VITEK 2 (Biomerieux, France) automated microdilution method was used in sensitivity tests.

Results

The mean age of 85 episodes included in the study was 3.49 (±5.4) years. 58% of the patients were male and 42% were female. 18.8% of the patients were premature. The most common service was newborn service (30.6%). Neutropenia was 26% and thrombocytopenia was 55% at the time of diagnosis. Klebsiella pneumonia was 93% and Klebsiella oxytoca was 7%. Carbapenem resistance rate was found to be 30.6% in Klebsiella spp. Carbapenem resistance was found 18% in 2014, 38% in 2015, 42% in 2016 and 25% in 2017. In patients who developed carbapenem-resistant Klebsiella infection, the duration of pre-hospitalization ≥14 days (P = 0.034), the absolute neutrophil count < 100 (P = 0.048) and steroid use (P = 0.025) were statistically significant risk factors. The mean length of hospital stay was 107 (±103) days. Klebsiella spp. attributable mortality due to infection was 14% and crude mortality was 15%. No statistically significant difference was found in patients who developed resistant and susceptible infections.

Conclusion

Carbapenem resistance in Klebsiella infections was increased. Prolonged hospital stay, neutropenia and steroid use in the last 3 months were identified as significant risk factors for carbapenem-resistant Klebsiella infections.

Disclosures

All authors: No reported disclosures.
2278. Emergence of Resistance and Associated Mortality during Persistent Pseudomonas aeruginosa Bacteremia in Hematopoietic Cell Transplant Recipients and Hematologic Malignancy Patients
Authors: Fontana Lauren , Hakki Morgan
Published: October 2019

Background

Pseudomonas aeruginosa (PSA) bacteremia causes significant mortality in patients with hematologic malignancies (HM) and hematopoietic cell transplant (HCT) recipients in part due to intrinsic and acquired resistance mechanisms. However, the incidence of developing resistance on therapy and the associated outcomes are poorly described. We characterize the emergence of resistance on therapy and describe the outcomes of PSA bacteremia in this population.

Methods

We conducted a retrospective review of adults with HM and HCT recipients who developed PSA bacteremia between January 2012 and April 2018. A bacteremic episode was characterized as ≤ 14 days from the first positive blood culture. Persistent bacteremia was defined as a positive blood culture ≥ 72 hours of appropriate antibiotic therapy. Susceptibility testing was performed with VITEK2. Isolates were classified as “sensitive,” “intermediate,” or “resistant” per standard criteria; “intermediate” and “resistant” results were considered “non-susceptible.”

Results

66 episodes of PSA bacteremia occurred in 59 patients. Among episodes in which a patient survived for ≥3 days, 8 (12.1%) met criteria for persistent bacteremia. Non-susceptibility to therapy developed in 5 of 7 episodes (71.4%) of persistent bacteremia; 1 did not have susceptibilities performed on both isolates. Patients with persistent bacteremia had a second positive blood culture within a median of 3.5 days. A concomitant visceral nidus of infection (pneumonia = 6, soft tissue = 1) (P = 0.005) was identified as the primary risk factor for persistent bacteremia. Risk factors for emergence of non-susceptibility could not be determined due low number of events. Infection associated mortality (IAM) (death ≤ 14 days) occurred in 12 (17.1%) of all episodes and 6 of 8 (75%) of persistent bacteremia. Persistent bacteremia was the only risk factor associated with IAM (P = 0.0002, RR 7.3).

Conclusion

Emergence of resistance to anti-Pseudomonal β-lactam antibiotics frequently occurs during treatment for persistent PSA bacteremia in HCT recipients and HM patients. Persistent bacteremia is associated with a visceral nidus of infection and was the only independent predictor of IAM.

Disclosures

All authors: No reported disclosures.
2279. Study of Prescribing patterns and Effectiveness of Ceftolozane–tazobactam (C/T): Real-world Analysis (SPECTRA): a multi-national, multicenter observational study
Authors: Soriano Alex , Puzniak Laura , Paterson David , Thalhalmmer Florian , Kluge Stefan , Viale Pierluigi , Kaul Sundeep
Published: October 2019

Background

C/T has demonstrated efficacy in randomized clinical trials to treat cIAI and cUTI and recently completed a study in ventilator-associated bacterial and ventilated hospital-acquired bacterial pneumonia. The purpose of this study was to evaluate the real-world clinical use and outcomes of C/T in a multi-national study.

Methods

SPECTRA is a multi-national, multicenter, retrospective, inpatient, observational study of patients treated with C/T in Australia, Austria, Germany, Italy, Spain and United Kingdom. Patients admitted with greater than 48 hours of C/T treatment were included. Demographics, clinical characteristics, treatment management patterns, microbiological findings and outcomes were analyzed.

Results

There were 155 patients from 20 participating hospitals in 6 countries. The average age was 58.0 years (±17.8) and most were male 114 (74%). The majority 130 (84%) had at least one comorbidity, with the most common being renal impairment 87 (56%), immunocompromised 62 (40%), and diabetes 52 (34%). The majority, 94 (61%), had previous hospitalizations ≥ 6 months prior to receiving C/T, of which 29 (31%) had an ICU stay and surgeries 64 (42%). Most patients 126 (82%) received antibacterials within 30 days of receiving C/T, 61 (40%) received carbapenems and 47 (31%) received aminoglycoside. The average duration of C/T was 15 (SD12) days. The source of infection was cUTI for 31 (20%), cIAI for 19 (12%) and respiratory for 43 (28%) of C/T treated patients. Most 107 (70%) had an ID consult with an average of 7 (SD 11.3) consults. The top pathogen was Pseudomonas 124 (81%) followed by E. coli 22 (14%), with 56 (37%) having a polymicrobial infection. Over half of the patients were in the ICU 84 (55%), 58 (38%) underwent at least 1 surgery, with 65 (48%) being related to the infection, 60 (39%) had sepsis and 21 (14%) had septic shock. All-cause in hospital mortality was 16%. 30-day all-cause readmission was 12% and 6% were infection related.

Conclusion

Despite the complexity of the patients in this real-world analysis, most C/T patients had beneficial outcomes that are similar to results of controlled clinical trials.

Disclosures

All authors: No reported disclosures.
2285. Emergence of perioperative antibiotic non-susceptible pathogens causing prosthetic joint infections in monomicrobial Gram-negative and polymicrobial infections.
Authors: Coyle Meredith M , Riederer Kathleen M , Hooshmand Babak , Youssef Dima , Bhargava Ashish
Published: October 2019

Background

Current recommendations by Infectious diseases society of America (IDSA) endorse cefazolin for perioperative use. What is less known currently is the emergence of resistance in Gram-positive (GP) and Gram-negative (GN) prosthetic joint infections (PJIs) in the setting of perioperative use of antibiotics.

Methods

A retrospective multi-centric cohort was studied at three hospitals from January 2012 to December 2018. Patients with PJIs were identified using ICD codes. We reviewed electronic medical records and identified PJIs which followed primary arthroplasties. We included cases where perioperative antibiotics records were available.

Results

66 infected PJIs with available preoperative records were included. 40 (61%) patients were females, and 42 (64%) were caucasians. Indications for undergoing arthroplasty were degenerative joint disease (DJD) in 52 (78%), trauma in 13 (20%) and avascular necrosis in 1 (1.5%). Sites for arthroplasty were knee in 33 (50%), hip 28 (42.5%), shoulder 4 (6%), and ankle in 1(1.5%). 43 (65%) had GP monomicrobial, 6 (9%) had GN monomicrobial and 17 (26%) had polymicrobial infections. 40 (60.5%) patients received cefazolin, 25 (38%) received vancomycin and 1 (1.5%) received ceftriaxone as perioperative prophylaxis. 7 (11%) PJIs among monomicrobial infections and 6 (35%) among polymicrobial infections had non-susceptible (NS) organisms (Figure 1 and 2). 8 (47%) polymicrobial PJIs had a mixed susceptibility profile with drug susceptible and resistant organisms.

Conclusion

In general, when monomicrobial GP pathogens are causative for PJI, current use of cefazolin as perioperative drug of choice is sound and we agree with the current perioperative recommendations. It should be recognized that in situations where the PJI is due to GN or is polymicrobial, resistance to perioperative antibiotics may be present at a greater rate. From this study we conclude that in cases where the pathogen is known to be GN or polymicrobial from a diagnostic aspiration, then a broader antibiotic selection may be of benefit perioperatively.

Disclosures

All authors: No reported disclosures.
2288. Role of Β Lactam-Β Lactamase Inhibitors in Indian Tertiary Care Hospitals: Results from a Nationwide Survey
Authors: Kamat Shweta , Gupta Pankaj , Mane Akshata
Published: October 2019

Background

Broad-spectrum antibiotics, particularly third-generation cephalosporins, are routinely used in the treatment of nosocomial infections. The emergence of Extended Spectrum Β-Lactamase (ESBL)-producing pathogens in Indian tertiary care hospitals warrants the need to reassess β-lactam–β-lactamase inhibitors (BL-BLIs) as better alternative treatments.

Methods

An online survey was conducted by Pfizer India to understand the usage of BL-BLIs across Indian hospitals. The survey was administered to 334 clinicians across multiple specialties out of which 195 were from tertiary care hospitals. Results were analyzed using MS-Excel statistical tools.

Results

One-hundred ninety-five (195) clinicians from tertiary care hospitals completed the survey. About 78% of HCPs revealed the resistance to third-generation cephalosporins (e.g., ceftriaxone, ceftazidime) to be between 10–60% in their clinical settings. BL-BLIs were mostly preferred for treatment based on hospital antibiograms (64%) and used as first-line options for hospitalized adults with mild-moderate severe infections caused by ESBL-producing organisms (71%) and in mild-moderate infections caused by susceptible Gram-negative bacteria such as Enterobacteriaceae (54%). The average duration of IV BL-BLI treatment was 5–7 days (66%). The HCPs considerations while choosing BL-BLIs were mainly based on anti-microbial spectrum (81%), and rationality of BL/BLI combination (63%) and clinical experience with the BL-BLI molecule (63%). Cefoperazone-Sulbactam (CS) and Piperacillin–tazobactam (PT) were most commonly prescribed BL-BLIs and HCPs preferred the latter for pneumonia (67%), skin and soft-tissue infections (57%), bloodstream infections (67%) and cancer-associated febrile neutropenia (64%); while they preferred former for urinary tract infections (64%). CS and PT were preferred for intra-abdominal infections (57% and 64% respectively) and post-surgical infections (56% and 53% respectively).

Conclusion

CS and PT were the most commonly prescribed BL-BLIs probably due to their wide antimicrobial spectrum, rationality of the BL/BLI combination and the clinical experience with the molecules. BL-BLIs are still a mainstay of treatment for infections due to ESBL producing organisms.

Disclosures

All authors: No reported disclosures.
2292. Incidence of Acute Kidney Injury Associated with Duration of Vancomycin and Piperacillin/tazobactam Combination Therapy
Authors: McMullen Lisanne , Craft Rachael , Tenkku Mackenzie
Published: October 2019

Background

Empiric antibiotic therapy for serious and healthcare-acquired infections often requires coverage for resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. These regimens commonly consist of vancomycin plus an antipseudomonal β-lactam. Recent studies have reported increased acute kidney injury (AKI) risk associated with concomitant vancomycin and piperacillin/tazobactam therapy compared with each agent alone. The objective of this study was to determine whether vancomycin with piperacillin/tazobactam had an increased AKI incidence compared with vancomycin plus cefepime or meropenem. Furthermore, data were analyzed to determine whether a specific duration was associated with an increased AKI incidence.

Methods

A retrospective cohort study was conducted analyzing patients who received vancomycin in combination with piperacillin/tazobactam (V+PT), cefepime (V+C), or meropenem (V+M) between January 1, 2018 through June 30, 2018. Adult patients with normal baseline renal function and receipt of at least 48 hours of combination therapy, with the two antibiotics initiated within 24 hours of one another, were included. AKI events, evaluated using the Acute Kidney Injury Network (AKIN) criteria, during antibiotic therapy and up to 72 hours after antibiotic discontinuation were recorded. This data were used to calculate the AKI incidence with each regimen and AKI incidence associated with each day of therapy.

Results

A total of 181 patients were included in the study. The incidence of AKI in the V+PT group was 22.8% vs. 5.6% and 16.7% in the V+C and V+M groups, respectively (P = 0.237). Median duration of therapy when AKI occurred was 3 days for V+PT, 4 days for V+C, and 2 days for V+M (P = 0.015). Patients in the V+M group received more nephrotoxic agents compared with V+PT and V+C (P = 0.004). Statistical analysis did not find a specific day of V+PT therapy predictive of AKI. However, a time to event analysis demonstrated a steady increase in AKI risk with V+PT from day 2 through 6.

Conclusion

Although not statistically significant, V+PT therapy was associated with a higher incidence of AKI compared with V+C or V+M. Future studies are needed to further assess the impact of duration of therapy on AKI incidence.

Disclosures

All authors: No reported disclosures.
2297. Epidemiology of Antibiotic-resistant Pathogens and Empiric Treatment Patterns in Community-Onset Sepsis
Authors: Rhee Chanu , Kadri Sameer S , Dekker John P , Danner Robert L , Chen Huai-Chun , Fram David , Klompas Michael
Published: October 2019

Background

Guidelines recommend immediate empiric broad-spectrum antibiotics for all patients with suspected sepsis. Understanding the epidemiology of antibiotic-resistant pathogens and empiric treatment patterns in sepsis could inform improvements in antibiotic utilization and outcomes.

Methods

We identified adults admitted during 2009–2015 to 104 US hospitals in the Cerner HealthFacts dataset who met CDC Adult Sepsis Event criteria and had positive clinical cultures within 2 days of admission. We characterized prevalence and empiric treatment rates for methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococcus (VRE), ceftriaxone-resistant Gram-negative organisms (CRO) (including P. aeruginosa), and extended-spectrum β-lactamase Gram-negative organisms (ESBL). We evaluated associations between in-hospital mortality and either inappropriate empiric therapy (antibiotics inactive against any isolated pathogen) or excessively broad therapy (empiric MRSA or VRE coverage, extended spectrum β-lactam, or carbapenem therapy when targeted organisms were absent), adjusting for baseline characteristics and severity-of-illness.

Results

The cohort included 17,962 patients with culture-positive sepsis; 2,965 (16.5%) died in-hospital. The most common culture-positive sites were urine (51.2%), blood (41.8%), and respiratory (16.5%). The most common pathogens were E. coli (33.0%), S. aureus (20.9%), and Streptococcus (13.2%) (Figure 1). Most (81.6%) patients received empiric antibiotics active against all isolated pathogens. Empiric therapy was directed at resistant organisms in 67.5% of cases (primarily vancomycin and extended spectrum β-lactams, Figure 2), but resistant organisms were isolated in only 25.2% (MRSA 11.5%, CRO 12.9%, VRE 2.0%, ESBL 0.8%). Both inappropriate empiric therapy and excessively broad empiric therapy were associated with higher mortality on multivariate analysis (OR 1.30, 95% CI 1.14–1.48 and OR 1.20, 95% CI 1.05–1.38, respectively).

Conclusion

Most patients with community-onset sepsis do not have resistant pathogens, yet empiric broad-spectrum antibiotics are frequently prescribed. Both inappropriate empiric therapy and excessively broad therapy are associated with worse outcomes.

Disclosures

All authors: No reported disclosures.
2300. Incidence, Complications, and Recurrence of Herpes Zoster in Unvaccinated Adults ≥50 Years of Age
Authors: Ackerson Bradley , Bruxvoort Katia , Sy Lina S , Luo Yi , Tanenbaum Hilary , Tian Yun , Zheng Chengyi , Cheung Bianca P , Patterson Brandon J , Van Oorschot Desiree , Fu Tseng Hung
Published: October 2019

Background

More recent baseline epidemiological data for Herpes Zoster (HZ) in adults ≥ 50 years of age, obtained before the introduction of the adjuvanted Recombinant Zoster Vaccine (RZV), are needed for future evaluations of the impact of RZV on HZ epidemiology.

Methods

The study comprised five elements: (1) The incidence of HZ was estimated from immunocompetent adults ≥ 50 years of age not vaccinated with Zoster Vaccine Live who had incident HZ between 2011–2015. HZ was identified by International Classification of Diseases (ICD) codes from electronic health records (EHR) of 4.6 million Kaiser Permanente Southern California members; (2) Postherpetic neuralgia (PHN) was identified by validated survey and medical record review of laboratory-confirmed incident HZ cases recruited during 2012–2015 for HZ-related pain ≥ 90 days after initial HZ diagnosis; (3) HZ Ophthalmicus (HZO) with ocular complications was identified by ICD codes and keyword search in EHR among patients identified with HZO using a validated natural language processing algorithm; (4) The proportion of HZ-related non-PHN and non-HZO cutaneous, neurological or other complications was assessed by double abstraction of EHRs from a sample of 600 incident HZ cases; (5) Recurrent HZ was identified by having an HZ diagnosis with HZ antiviral medication ≥ 6 months after the most recent HZ diagnosis with HZ antiviral medication in a cohort initially diagnosed with HZ between 2007 and 2008 and followed through 2016.

Results

We identified 40,893 incident HZ cases with an overall incidence of 9.92 (95% confidence interval [CI]: 9.82–10.01) per 1000 person-years. The proportion of incident HZ cases with PHN and HZO with ocular involvement was 18.37% (95% CI: 14.90–21.84%) and 8.06% (95% CI: 7.80–8.32%), respectively. The proportion of cutaneous, neurological, and other complications was 7.20% (95% CI: 5.44–8.96%), 0.87% (95% CI: 0.79–0.95%), and 1.24% (95% CI: 1.15–1.33%), respectively. The incidence of recurrent HZ was 10.96/1000 person-years (95% CI: 10.18–11.79).

Conclusion

HZ is common among unvaccinated US adults ≥ 50 years of age, with PHN and HZO occurring most frequently among incident HZ cases.

Funding

GlaxoSmithKline Biologicals SA, GSK study identifier: HO-17-18378.

Disclosures

All authors: No reported disclosures.
2301. Increased Risk of Varicella-Associated Hospitalizations Among Adult Immigrants From Temperate and Tropical Countries After the Introduction of a Childhood Varicella Vaccination Program in Quebec, Canada
Authors: Mah Jordan , Lieu Anthony , Greenwald Zoë R , Akaberi Arash , Song Sunny , Azoulay Laurent , Brisson Marc , Quach Caroline , Greenaway Christina
Published: October 2019

Background

Varicella zoster virus (VZV) hospitalizations are an uncommon, severe and costly consequence of VZV. Childhood VZV vaccination leads to decreased VZV rates across all age groups through herd immunity but increases the age of VZV acquisition and the potential risk of severe VZV in non-immune adults. A large proportion (~15%) of young adult immigrants from tropical regions are susceptible to VZV due to different transmission dynamics in their countries of origin and lack of vaccination. We aimed to describe the impact of the childhood VZV program introduced in 2006 in Quebec on VZV hospitalizations in immigrants and nonimmigrants.

Methods

A population-based cohort of all medically-attended VZV cases in Quebec, Canada (1996–2014) were identified in administrative health databases and linked to immigration data. VZV-attributable hospitalizations included those with primary or secondary ICD-9 or ICD-10 codes for VZV. Overall age-standardized and age-specific rates of hospitalizations were calculated during pre- (1996–98), private (1999–2005) and public vaccination (2006–14) periods and by immigrant status and pregnancy. Relative risk (RRI-NI) and 95% CI for immigrants vs. nonimmigrants were estimated.

Results

5873 hospitalizations occurred among 230,052 VZV cases. Hospitalization rates decreased dramatically in the pre to public vaccination period (6.6 to 1.3/100,000 population); however, the proportion of hospitalized varicella cases increased from 1.7% to 3.9% (P < 0.01). Immigrants only accounted for 3.6% of hospitalizations (N = 213) however, the proportion of all hospitalizations among immigrants increased in the pre- vs. public-vaccination periods in those aged 10–19 years (2.9% to 13.7%) and 20–39 years (8.8% to 22.7%). The RR was higher in these age groups in the public vaccination period [RRI-NI 1.96 and RRI-NI 1.67] (Table 1). Adults (>20 years) accounted for 52% (CI: 45–59%) and pregnant women 18% (13–25%) of all hospitalizations among immigrants compared with only 14% (13–15%) and 1.6% (1.3–2.0%) in nonimmigrants, respectively.

Conclusion

Young adult and pregnant immigrants bore a disproportionate burden of VZV hospitalizations after the introduction of childhood VZV vaccination. Susceptible immigrant adults would benefit from targeted VZV vaccination.

Disclosures

All authors: No reported disclosures.
2304. Incidence and Risk Factors for Herpes Zoster among Diabetes Patients at Siriraj Hospital; Results from a 10-year Cohort
Authors: Chuanchaiyakul Nalinee , Thongtang Nuntakorn , Rattanaumpawan Pinyo
Published: October 2019

Background

Herpes Zoster (HZ) is the reactivation of latent varicella-zoster virus. Diabetes Mellitus (DM) is one of well-known risk factors for HZ. Nowsday, the knowledge on the incidence of and risk factors for HZ among Thai DM patients is limited.

Methods

We conducted a nested case–control study of DM patients who attended the Siriraj DM clinic for ≥6 consecutive months during 2005–2014. Eligible subjects were identified through the DM clinic registry database (n = 1,427). Cases were those who had ≥1 episode of HZ while controls were those without evidence of HZ during the study period. We captured 40 cases and randomly sampled 175 controls (1 case: 4 controls). All data were obtained via chart-review, the ICD-10, pharmacy and laboratory databases

Results

During the 10-year study period, the cumulative incidence and the incidence rate of HZ were 0.28% [95% CI: 0.20–0.38%] and 3.96 [95% CI: 2.90–5.28] per 1,000 person-years. The most common sites were trunk (27.5%), followed by herpes opthalmicus (22.5%). Thirty-five percent had post-herpetic neuralgia and only 1 case required hospitalization. Independent risk factors for HZ [adjusted odd ratio; 95% CI; P-value] identified from multivariate analysis included underlying hypertension [3.48; 1.28–9.43; P = 0.01], number of hypoglycemic drug used [1.46; 1.03–2.08; P = 0.04] and previous use of herbal remedies [3.83; 1.06–13.84; P = 0.04]. Furthermore, higher body mass index was an independent protective factor [0.89;0.81–0.98; P = 0.02].

Conclusion

The incidence rate of HZ among DM patients at our institute was comparable to other Asian countries. Risk factors for HZ can be used to identify patients who would benefit the most from preventive interventions.

Disclosures

All authors: No reported disclosures.
2313. Influenza and Respiratory Syncytial Virus (RSV) Surveillance in the US Department of Veterans Affairs (VA): 2018–2019 Season
Authors: Lucero-Obusan Cynthia , Schirmer Patricia , Oda Gina , Holodniy Mark
Published: October 2019

Background

VA conducts ongoing surveillance for viral respiratory infections, notably influenza and more recently RSV. VA’s large elderly population is at higher risk for influenza and RSV complications, including hospitalization and death. Herein we summarize VA’s 2018–19 national surveillance data.

Methods

Influenza telephone triage, influenza-like-illness (ILI) encounters and antiviral prescriptions plus outpatient visits, laboratory testing (antibody tests excluded), hospitalizations and deaths for both influenza and RSV were obtained from VA data sources (9/30/18–3/31/19) and compared with prior seasons. Influenza vaccinations were captured starting 8/1/2018. Vaccination rates were calculated based on VA users during the fiscal year.

Results

Surveillance metrics are presented (Table, Figure). ILI visits ranged from 0.9%-3.3% during the season. RSV peaked earlier than influenza (Week 1 vs. Week 11). Testing revealed 1,674 RSV positives out of 31,404 tests performed (5.3%) and 15,052 influenza positives out of 105,760 tests performed (14.2%). We identified 22 cases of RSV and influenza co-infection (positive test results on the same date or within 3 days). 22% of laboratory-confirmed influenza cases were hospitalized (same proportion as the prior season) while 35% of RSV cases were hospitalized. Median length of stay was longer for RSV hospitalizations (4 days vs. 3 days for influenza).

Conclusion

The 2018–2019 influenza season was less severe than the 2017–2018 season, and most like the 2016–2017 season. 2018–2019 saw relatively little Influenza B in VA patients, despite elevated activity into the spring. High-dose/adjuvanted vaccine administration increased over the seasons evaluated. RSV surveillance for 2018–2019 demonstrated an earlier peak in activity and the percentage of patients with laboratory-confirmed RSV who were hospitalized and died during their hospitalization was higher compared with influenza. Although fewer RSV tests were performed and testing practices were variable across VA facilities, the weekly trend aligned closely with influenza. Surveillance for both viruses is important in VA given their associated morbidity and mortality.

Disclosures

All authors: No reported disclosures.
125. The Clinical Impact of 16S rRNA Bacterial Sequencing in Infective Endocarditis
Authors: El-Dalati Sami , Cinti Sandro , Owczarczyk Anna , Riddell Jamie , Fagan Christopher , Chanderraj Rishi , Fukuhara Shinichi
Published: October 2019

Background

Cases of possible and/or culture-negative endocarditis continue to be a diagnostic challenge. Performing bacterial 16S ribosomal RNA polymerase chain reaction (rRNA PCR) sequencing on cardiac valves now allows providers to make microbiologic diagnoses that were previously unobtainable (sensitivity 66–80.5%). However, few publications address how the PCR results impact clinical management in endocarditis patients.

Methods

Between July 1, 2014 and December 31, 2018, the results of all 16S rRNA PCR tests collected from cardiac valves at the University of Michigan were reviewed. Samples were sent to the University of Washington for sequencing. Each chart was then reviewed by two independent ID physicians to determine whether patients’ medical plans were impacted by the PCR results.

Results

41 patients were identified with associated 16S rRNA PCR testing from cardiac valves. 16 cases met Duke Criteria for definite endocarditis, 22 for possible and 3 were rejected endocarditis. Overall, 18 (43.9%) samples were positive. Of these, 10 patients had concordant positive blood cultures. In 8 patients a previously unsuspected organism was identified. Twenty-four out of 41 patients were considered to have culture-negative endocarditis with October 24 (41.7%) who had positive PCR results. Twenty-two patients were noted to have operative findings consistent with infection with 16 (72.7%) having corresponding positive PCR results. 4/41 (9.8%) patients had their management plans changed based solely on the PCR findings. In 23/41 (56.1%) cases the PCR result was never referenced by any medical provider in the electronic medical record. There were 7 (17.1%) cases where patients received 6 weeks of antibiotics despite presenting with possible culture-negative endocarditis, noninfectious operative findings and negative valve PCRs which were not reviewed.

Conclusion

16S rRNA PCR sequencing is a useful tool for obtaining a microbiologic diagnosis in cases of possible or culture-negative endocarditis. The test has significant potential to impact individual patient care and in a subset of cases may be used to de-escalate antibiotic therapy. However, testing delays and cumbersome resulting methods impede bacterial sequencing from reaching its full potential as a diagnostic modality.

Disclosures

All authors: No reported disclosures.
2325. Relationship Between Neighborhood Census-Tract-Level Poverty and Respiratory Syncytial Virus Infection in hospitalized Adults in the San Francisco Bay area, CA 2015–2017
Authors: Holmen Jenna , Cikesh Bryanna , Kim Lindsay , Reingold Art
Published: October 2019

Background

In the United States, respiratory syncytial virus (RSV) is a leading cause of admission for adults with respiratory illness. In adults > 50 years of age, it accounts for up to 12% of medically-attended acute respiratory illnesses and has a case fatality proportion of ~6–8%. Poverty can have an important influence on health. Few studies have evaluated the relationship of RSV incidence and poverty level, and no identified studies have evaluated this relationship among adults. We evaluated the incidence of RSV-associated hospitalizations in adults in the San Francisco Bay Area, CA by census-tract-level poverty.

Methods

Medical record data abstraction was conducted for all adults with a laboratory-confirmed RSV infection who were admitted to a hospital within the 3 counties comprising the catchment area (Alameda, Contra Costa, and San Francisco counties) during the 2015–2016 and 2016–2017 RSV seasons. Patient addresses were geocoded to their corresponding census-tract (CT). Census tracts were divided into four levels of poverty based on American Community Survey data of percentage of people living below the poverty level: 0–4.9%, 5–9.9%, 10-–9.9%, and ³20%. Incidence rates were calculated by dividing the number of RSV cases in each CT poverty-level (numerator) by the number of adults living in each CT poverty level (denominator), as determined from the 2010 US census, and standardized for age.

Results

There were 526 RSV case-patients with demographic characteristics as outlined in Table 1. The highest incidence of RSV-associated hospitalization was in CTs associated with the highest levels of poverty (>20%). However, the second highest incidence of RSV-associated hospitalization occurred among adults living in CTs with <5% poverty (Figure 1 and Table 2).

Conclusion

The incidence rate of RSV-associated hospitalization in adults appears to be positively correlated with highest census-tract level of poverty; however, there is a high incidence among adults living in the lowest poverty census-tracts.

Disclosures

All authors: No reported disclosures.
2338. Early Predictors of Mortality in Neonatal Disseminated Herpes Simplex Virus Infection
Authors: Ouellette Christopher , Mejias Asuncion , Shimamura Masako , Marzec Laura , Salamon Doug , Leber Amy , Sanchez Pablo J
Published: October 2019

Background

Disseminated neonatal herpes simplex virus (dHSV) infection is associated with substantial morbidity and an estimated case fatality rate of ~25% despite antiviral therapy. Contemporary data on predictors of mortality among infants with dHSV infection are limited.

Methods

From January 2012 to December 2018, neonates with HSV infection were identified by the Virology database at Nationwide Children’s Hospital. Demographic, clinical, laboratory, and radiographic data were obtained from the infants’ electronic healthcare records to identify cases of dHSV infection and to determine possible predictor(s) of mortality. dHSV was defined as detection of HSV DNA by polymerase chain reaction (PCR) in blood, cerebrospinal fluid, or skin/eye/mouth, and evidence of hepatitis, pneumonitis, sepsis, or coagulopathy, with or without central nervous system involvement.

Results

Of 43 neonates with HSV infection, 12 (28%) infants (median [IQR] age: 8.5 [7–11] days) had dHSV and 6 (50%) died. Clinical and laboratory findings of neonates who survived vs. those who died are presented in Table 1. The median duration of symptoms at presentation was 1.5 [1–2] days. Among infants who died, the median duration of hospitalization to time of death was 1.5 days (range, 0 to 4 days). Clinical signs at presentation and blood semiquantiative viral loads (cycle threshold, Ct) were not different between infants who survived (Ct 18.0 [15.4–23.3]) and those who died (16.6 [13.4–23.3]; P > 0.05). Initial serum alanine aminotransferase (ALT), INR or lactate were not different between the two groups. However, initial serum median albumin concentration was lower among those who died vs. survivors (1.8 g/dL vs. 2.7 g/dL, P = 0.004). To assess the sensitivity and specificity of potential laboratory predictors of mortality, serum laboratory values were evaluated as follows (sensitivity, specificity): ALT > 800 (67%, 80%), INR > 2.7 (67%, 80%), serum lactate > 3 mmol/L (80%, 100%), and initial serum albumin < 2 g/dL (100%, 100%).

Conclusion

Albumin concentrations < 2 g/dL at presentation correlated highly with mortality in neonatal dHSV infection, suggesting that hypoalbuminemia may reflect components of both viral sepsis and poor synthetic liver function. Larger cohorts of neonates with dHSV infection are needed to confirm this result.

Disclosures

All authors: No reported disclosures.
2339. Clostridioides difficile: Impact of Active Screening of Asymptomatic Carriers and Testing Stewardship
Authors: Beth Graham Mary , Buchan Blake W , Singh Siddhartha , Revolinski Sara , Ledeboer Nathan A , Huerta Susan M , Pintar Paula , Savage Sabrina , Behrens Elizabeth , Munoz-Price L Silvia
Published: October 2019

Background

We recently implemented a hospital-wide C. difficile testing algorithm and screening/isolation of C. difficile asymptomatic carriers primarily in heme-onc units. We aim to evaluate the impact of these interventions on the epidemiology of C. difficile + tests.

Methods

This retrospective cohort was performed in a 600-bed hospital in Milwaukee, WI, from January 1, 2016 to March 31, 2019. All clinical C. difficile tests included nucleic acid amplification (NAAT; Xpert C. difficile, Cepheid). On February 2017, all NAAT+ tests had toxin (tox) checked (Quick check complete, Alere). Testing algorithm (Figure 1) started mid 2016 until now. Screening phases included: Phase 1 (September 2016–May 2017): C. difficile screening cultures shared with units but not placed in electronic medical records (EMR). Patients + placed on enteric precautions (gown, gloves, hand hygiene). Phase 2 (May 2017–January 2018): C. difficile screening (NAAT) performed on admission and weekly thereafter, results placed in EMR, NAAT+ patients placed on enteric precautions. Phase 3 (January 2018–present): C. difficile screening (NAAT) on admission, results placed in EMR, NAAT+ patients placed on enteric precautions. Federal reporting changed to only reporting NAAT+tox+. Tests (NAAT+, NAAT+tox+, and NAAT+tox-) were analyzed using Poisson regression offsetting for log of patient-days using SAS, v9.4.

Results

Hospital-wide C. difficile tests decreased from 21 to 10.9 tests per 1,000 patient-days (P < 0.0001; Figure 2). This effect was seen in heme-onc units (41 to 15.7; P < 0.0001; Figure 3) and in all other units (18.9 to 9.9; P < 0.0001). All NAAT+ results decreased from 2.99 to 1.94 per 1,000 patient-days hospital wide (P < 0.0001) but remained unchanged in heme-onc units (4.6 to 3.7, P > 0.05). NAAT+tox+ results remained unchanged hospital wide and in heme-onc units (0.8 to 0.7 and 1.1 to 1.2, respectively; both P > 0.05); however, the frequency of NAAT+tox− tests decreased hospital wide (1.8 to 1.3; P = 0.0003) and in heme-onc units (3.8 to 2.4; P = 0.05).

Conclusion

A C. difficile testing algorithm was successful decreasing the number of C. difficile tests performed and had a hospital-wide reduction of NAAT+tox− tests. The rate of NAAT+tox+ cases in heme-onc units and hospital wide remained unchanged despite active screening and isolation in selected units.

Disclosures

All authors: No reported disclosures.
2342. Elimination of Reflexive C. difficile PCR Testing Among Inpatients Resulted in Cost Savings Without Adverse Events
Authors: Sullivan Eva , Majumdar Rohit , Ortiz Courtney , Riggs Patricia K , Crum-Cianflone Nancy
Published: October 2019

Background

Diagnosis of C. difficile infection is imperfect and various algorithms have been proposed. While PCR is sensitive for detecting toxin-carrying C. difficile, it leads to overdiagnoses resulting in antibiotic overuse and potentially unnecessary healthcare costs.

Methods

We performed a study of C. difficile cases after changing the testing protocol from reflexive vs. physician-requested PCR in cases of indeterminant EIA testing (antigen +, toxin −). The study was conducted among inpatient adults at four large hospitals in the southern California area and evaluated two 6-month periods: pre-intervention: (September 5, 2016–March 5, 2017) and post-intervention (3/6/2017–9/6/2017). Only the first C. difficile test during a period per patient was evaluated. Primary outcome was change in number of C. difficile diagnoses. Secondary outcomes included adverse events (missed cases of C. difficile and 30-day readmissions) and cost savings (accounting for PCR, isolation, and treatment costs).

Results

A total of 500 EIA indeterminant C. difficile test results were evaluated, 281 pre- and 219 post-intervention. There were no statistically significant differences in demographics, laboratory values (WBC, Cr), or hospital site between the study periods. A PCR was performed in 99.6% (280/281; one not performed due to an inhibitor) and 66% (144/219) in the pre- vs. post-intervention periods (P < 0.01); the PCR was positive in 65% (n = 182 and n = 94, respectively) in both periods. The change in testing strategy resulted in a 49% reduction in PCR testing and 48% fewer C. difficile cases. There were no differences between study periods in 30-day readmissions for all-cause (P = 0.96), GI-related illness (P = 0.93) or C. difficile (P = 0.47), nor in new or recurrent C. difficile cases (P > 0.99). No patient without a PCR and not treated was later diagnosed with C. difficile infection. Each reflexive PCR avoided led to a cost savings of $4,384/patient.

Conclusion

Diagnostic stewardship is an emerging area that can potentially reduce overdiagnosis and overtreatment of a variety of infectious diseases. Our study showed that changing C. difficile PCR testing among EIA-indeterminant cases from reflexive to requiring a physician order resulted in valuable cost savings without associated adverse events.

Disclosures

All authors: No reported disclosures.
2347. Impact of Multidisciplinary Review of Clostridioides difficile Testing
Authors: Foreman Jena , Belter Neha , Thannum Stephanie
Published: October 2019

Background

Minimizing Clostridioides difficile infections (CDI) is an important patient safety goal due to significant cost and disease burden with CDI causing 15,000 deaths annually in the United States. Diagnosis of CDI is complicated when DNA amplification assay will return positive for both colonization and active infection of C. difficile, so testing clinically symptomatic patients with at least 3 loose stools per day is paramount to obtaining accurate reporting rates and starting proper treatment for CDI.

Methods

Due to economic considerations, the study was a single-center retrospective review of inpatients ≥ 18 years old who had C. difficile tests ordered from November 2017 to February 2019. Baseline characteristics collected include age, sex, white blood cell (WBC) count, fever, past C. difficile infections, recent antibiotic use, recent laxative use, and tube feeding status. Data were analyzed using descriptive statistics. The primary objective of this study was to look at the appropriateness of C. difficile tests pre and post-implementation of multidisciplinary review. Criteria for appropriateness of testing included 3 or more loose stools in addition to one additional factor including fever, elevated WBCs, immunocompromised status, or severe sepsis/septic shock. Secondary objectives include evaluating hospital-onset CDI rates and cost analysis.

Results

Baseline characteristics were similar between the two groups with the exception of statistically fewer patients with 3 or more liquid stools found in the post-implementation group (P = 0.0003). After implementation of a multidisciplinary review, the number of C. difficile tests ran significantly declined from 79% to 56% (P = 0.0001). The number of negative tests also were significantly reduced from 60% to 43% (P = 0.0001), with patients who had less than 3 stools per day being tested less frequently in the post-implementation group. Inappropriate test avoidance resulted in an annual savings of $1,550 in testing supplies alone, not including isolation or labor costs. There was no significant difference in hospital-onset CDI.

Conclusion

Implementation of a multidisciplinary review of C. difficile testing avoids clinically inappropriate tests and results in cost savings with no effect on incidence of hospital-onset CDI.

Disclosures

All authors: No reported disclosures.