bluuebunny/crossref_metadata_2025 huggingface dataset:
112. Impact of Respiratory Viral PCR Panels (RVP) and Serum Procalcitonin (PCT) on Antibiotic Days of Therapy (DOT) in Patients Admitted with Lower Respiratory Tract Infections (LRTI)
Authors: Bilinskaya Anastasia , Kuti Joseph L , Linder Kristin
Published: January 2021

Background

IDSA advocates for the use of RVP and PCT to reduce inappropriate antibiotic use. These assays were implemented in our health system without formal antimicrobial stewardship intervention. Herein, we evaluated assay utilization and impact on antibiotic DOT in patients admitted with LRTI.

Methods

Records of patients admitted to our health system in January 2019 with a diagnosis of LRTI (ICD 10 codes: J13-22, J44, or J85) were reviewed. Patients < 18 years old, receiving active treatment at time of admission for a concurrent infection, or had a RVP or initial PCT ordered > 48 hours from admission were excluded. Patients were cohorted based on at least one test ordered (VPPC) vs neither (CTRL). The primary endpoint was total antibiotic DOT, including inpatient and outpatient. Secondary endpoints were hospital length of stay (LOS), 30 day readmission (30DR), and all cause mortality (ACM). Multivariate linear regression was used to determine variables associated with DOT.

Results

Of 294 patients included, 15 (5.1%), 84 (28.6%), and 43 (14.6%) had RVP alone, PCT alone, or both ordered, respectively, resulting in 142 (48.3%) patients in the VPPC group. Providers modified therapy based on PCT and RVP results in 39.4% (50/127) and 33.3% (7/21) of patients, respectively. Median (IQR) DOT was similar between VPPC and CTRL groups (7 [5–9] vs 7 [3–8] days; p=0.159), respectively. Inpatient DOT (4 [2–5] vs 3 [2–4] days; p=0.001) and LOS (99.5 vs 81.7 hours; p=0.001) were longer in the VPPC group. VPPC patients were more likely to receive anti-pseudomonal B-lactams (anti-PSA) (26.8 vs 16.4%; p=0.044) and anti-MRSA antibiotics (45.1 vs 34.9%; p=0.096). No difference in 30DR (13.4 vs 15.1%; p=0.793) or ACM (2.1 vs 3.3%; p=0.794) was observed. Variables significantly associated with increased DOT were non-ICU admission, positive chest X-ray, LOS, younger age, and receipt of anti-MRSA or anti-PSA antibiotics.

Conclusion

Over one month, RVP or PCT was ordered in nearly half of admitted LRTI patients in our health system, but modification of therapy based on results was infrequent. The unrestricted use of these tests without stewardship intervention did not impact overall antibiotic DOT, LOS, 30DR, or ACM. These data emphasize the need for additional intervention to enhance the clinical utility of these tests.

Disclosures

Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))
1389. Economic Evaluation of Universal Varicella Vaccination in Mexico
Authors: Chacon-Cruz Enrique , Meroc Estelle , Costa-Clemens Sue Ann , Verstraeten Thomas
Published: January 2021

Background

Universal varicella vaccination (UVV) has proven to be cost-effective in countries where implemented. However, this has not yet been evaluated for Mexico. We assessed the cost-effectiveness of UVV in the Mexican Immunization Program from both healthcare and societal perspectives.

Methods

The annual disease burden (varicella cases/deaths, outpatient visits, and hospitalizations) were derived from Mexican seroprevalence-published data adjusted to the 2020 country’s population. The annual economic burden was calculated by combining disease with Mexican published unit cost data. Four different vaccination strategies were evaluated: 1. One dose of a single varicella vaccine at 1 year old; 2. Two doses of single varicella vaccine at 1 and 6 years; 3. One dose of a single varicella vaccine at 1 year, and quadrivalent measles-mumps-rubella-varicella vaccine (MMRV) at 6 years; 4. Two doses of MMRV at 1 and 6 years.

We developed an economic model for each vaccination strategy where 20 consecutive birth cohorts were simulated. The impact of vaccination (number of avoided cases/deaths) was evaluated for a 20 years follow-up period based on vaccine effectiveness (87% and 97.4%), and assuming a 95% coverage. Subsequently, we estimated net vaccination costs, benefit-cost ratio (BCR), annual costs saved, cost-effectiveness ratio.

Results

From annual disease burden estimation, avoided cases with one dose, and two doses were of 20,570,722 and 23,029,751, respectively. From the 20 years cohort, the yearly number of varicella cases was estimated at 2,041,296, and total costs at $115,565,315 (USD) (healthcare perspective) and $165,372,061 (healthcare and societal perspectives). Strategies 1 and 2 were found to be cost-saving (BCR >1) (Figure 1), and strategy 3 to be cost-effective (CE) ($1539 per Life Year Gained). Strategy 4 was not CE. Strategies 1 and 2 would allow saving annually $53.16 million and $34.41 million, respectively, to the Mexican society.

FIGURE 1

Conclusion

1.The disease and economic burden of varicella in Mexico are high.

2.UVV with four different vaccination strategies results in a high reduction of cases.

3.From healthcare and societal perspectives, UVV was shown to be cost-effective (with strategy 3), and cost-saving (with strategies using one dose or two doses separately).

Disclosures

All Authors: No reported disclosures
1391. Enhanced Education and Administration of Influenza Vaccine in a Pediatric Subspecialty Practice
Authors: McCarthy Carol A , Carson Leslie L , Russell George H , Lucas F L
Published: January 2021

Background

Strategies to increase influenza (flu) immunization rates are desirable. Some children who are at increased risk for severe disease may only be seen in a subspecialty office during the months when flu vaccine is offered. Subspecialists may also provide education for families that are uncertain about benefits of vaccines.

Methods

During the 2019- 2020 season, our multispecialty pediatric practice, which includes divisions of Endocrinology, Gastroenterology, Infectious Disease, Nephrology, Pulmonary, and Surgery, initiated a quality project to increase delivery of flu vaccine during visits. Beginning 10/1/19, providers were encouraged to use tools in the electronic medical record (EMR) to ask about flu vaccine status and administer if indicated and accepted. Flu immunizations given for all divisions, as well as individual divisions, were compared with the previous 2018–2019 season.

Results

From 9/1/19 -3/31/20, 615 doses of flu vaccine were administered for 5667 patients for a rate of 10.9 %. This was an increase from 9/1/18- 3/31/19 when 256 doses were given for 5760 patients (4.4%, p< .0001). All divisions had a significant increase in flu vaccine rates except for infectious disease. Review of certain high risk disorders showed significant increased rates for diabetes and asthma but not for inflammatory bowel disease, HIV infection, chronic renal disease, or cystic fibrosis. During this project an EMR flu tool was not used for 1788 patients (32%). Of the remaining 3879 patients, 1982 (51%) reported prior receipt of flu vaccine and 579 (15%) were not eligible for state supplied vaccine. For 1318 eligible patients, flu vaccine was accepted by 631 (48%) and given to 615 patients. Flu vaccine was declined by 687 (52%) patients.

Conclusion

There is opportunity to provide education and flu vaccine during pediatric subspecialty visits. All specialties increased the number of flu vaccine given except for infectious disease. This is likely because this division has routinely offered flu vaccine and visits for travel declined in 2020. Although the practice overall gave more flu vaccine from the prior year, there appear to be missed opportunities. Further quality improvement work will strengthen the EMR flu screening tools to increase participation and learn more about why flu vaccine is declined.

Disclosures

All Authors: No reported disclosures
1395. Influenza B-Associated Pediatric Mortality in the US Between 2010 and 2019
Authors: Bandell Allyn , Piedra Pedro , Ambrose Christopher S , Jhaveri Ravi , Jhaveri Ravi
Published: January 2021

Background

To assess the contribution of influenza B to mortality in the US pediatric population, we analyzed the proportion of influenza-associated pediatric mortality attributed to influenza A and B over nine influenza seasons using national surveillance data. The effectiveness of influenza vaccines against influenza B in the pediatric population was also assessed.

Methods

The study period was the 2010/11 to 2018/19 influenza seasons. Proportions of circulating strains in the general population and influenza-associated pediatric mortality for each season were obtained from annual Centers for Disease Control and Prevention Morbidity and Mortality Weekly Reports on influenza. A Chi-squared test with Yates’ correction was used to assess the contribution of influenza B to pediatric mortality relative to its circulation among influenza viruses. Consolidated vaccine effectiveness (VE) against influenza B for inactivated influenza vaccine (IIV) in the 2010/11 to 2017/18 seasons and live attenuated influenza vaccine (LAIV) in the 2010/11 to 2015/16 seasons were obtained from a published meta-analysis and annual US Flu VE Network studies. There were no US data on LAIV VE for 2016/17 and 2017/18.

Results

During the 2010/11 to 2018/19 seasons, influenza B accounted for 4.0%–29.2% of all circulating influenza strains. A/H3N2 viruses were the predominant circulating strain in most seasons. In the same period, influenza B accounted for 7.0%–54.1% of pediatric influenza-associated mortality (Figure). The proportion of influenza B-related deaths was significantly higher (p< 0.01) than what would have been expected based on the proportion of circulating influenza B strains in the general population, overall and in the 2010/11, 2012/13, 2016/17, and 2017/18 seasons. Point estimates of VE against influenza B for children aged 2–17 years ranged from 33%–70% for IIV between 2010/11 and 2017/18, and from 53%–82% for LAIV between 2010/11 and 2015/16.

Proportion of circulating influenza B strains compared with influenza B-associated pediatric mortality in the US between the 2010/11 and 2018/19 seasons

Conclusion

During the study period, influenza B accounted for a disproportionate percentage of pediatric mortality in the US relative to its overall circulation. These data counter the perception that influenza B is less severe than influenza A in children and highlight the importance of influenza vaccination to prevent influenza and its complications.

Disclosures

Allyn Bandell, PharmD, AstraZeneca (Employee, Shareholder) Pedro Piedra, MD, Roche (Consultant)Shionogi (Grant/Research Support) Christopher S. Ambrose, MD, MBA, AstraZeneca (Employee, Shareholder) Ravi Jhaveri, MD, AbbVie (Grant/Research Support)Alios (Research Grant or Support)Gilead (Grant/Research Support)Medimmune/AstraZeneca (Employee)Merck (Grant/Research Support)Saol Therapeutics (Consultant)Seqirus (Consultant)
1396. Live Virus Vaccination Following Pediatric Liver Transplantation: Results from Two Academic Children’s Hospitals
Authors: Newman Alexander M , Posch Leila C , Gianchetti Lauren , Rand Elizabeth B , Mohammad Saeed , Downes Kevin J , Muller William J
Published: January 2021

Background

Guidelines for immunization following solid organ transplantation discourage live virus vaccination (LVV) in most recipients. Single-center studies support LVV as safe and effective in orthotopic liver transplant (OLT) recipients on steroid-free immunosuppression (IS). We retrospectively evaluated LVV after OLT at 2 pediatric hospitals.

Methods

Records from OLT recipients between Jan 2007 and Dec 2017 at Lurie Children’s (Chicago) and Children’s Hospital of Philadelphia were reviewed. Patients who underwent OLT at either institution, had ≥ 2 years of follow up, and had documentation of vaccination prior to OLT were included. Adverse events (AEs) within two weeks of receipt of LVV were captured. Factors that might influence the selection of patients for LVV were reviewed, including choice, dose, frequency, and levels of IS medications. IS in non-vaccinated patients was compared to vaccinated patients at two year post-transplant follow-up in both groups using Chi-Square and T-test.

Results

Data from 249 patients met inclusion criteria. Varicella zoster (VZV) vaccine was given at least once to 92 patients post-transplant, and MMR to 91 (Table 1). Compared to patients who were re-vaccinated after transplant, those who received their first LVV after OLT were transplanted at a younger age (0.8 v 2.2 years) and received LVV sooner post-OLT (649 v 907 days). AEs were rare for either LVV: 2 experienced injection site reaction, 2 localized rash, and 1 had fever. One recipient experienced worsening rejection one month after MMR and received IV steroids and increased IS, but had no clinical findings concerning for viral infection from vaccination. Most LVV recipients were on a single IS agent both at time of LVV and 2 year post-OLT (Table 2), with tacrolimus the most frequent agent. Compared to those that did not received LVV post-OLT, those that did were on one IS agent more often. Tacrolimus levels were similar among patients receiving LVV post-OLT compared with those who did not.

Table 1

Table 2

Conclusion

In a series of pediatric OLT recipients, post-OLT LVV was generally safe and well tolerated. Patients who received LVV post-OLT were more often on one IS agent at 2 year follow up compared to those who did not. Our study supports prospective efforts to define guidelines for patients who may safely receive LVV after OLT.

Disclosures

Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support)
1398. Maternal Knowledge and Perceptions about Routine Immunisation in a Slum Area of Pakistan
Authors: Mustafa Ghulam , Mustafa Abdul Mannan
Published: January 2021

Background

To know the baseline coverage and potential obstacles for children vaccination before starting a health awareness program.

Methods

A cross sectional study on immunization coverage in the slum area of Multan, Pakistan was conducted and a total of 312 mothers were interviewed face to face for Knowledge, Attitudes, and Perceptions (KAP).

Results

Among the children less than 3 years, 33 % fully, 46 % partially and 21 % were not at all immunized. High levels of BCG and OPV zero rates (79%) and low rates of OPV3/DPT3 (48%) and measles (41%) vaccines were found. Majority of the mothers were satisfied with the program. Most of the mothers were aware about the importance of vaccination but were ignorant for the need to complete the schedule. There were many misconceptions and beliefs among the mothers of partial and unimmunized children. The majority were of view that vaccines contain ingredients that will make the children infertile.

Conclusion

There is a need to enhance the maternal knowledge about the vaccine preventable diseases and importance of completing the immunization schedule. Also the misconception about the vaccines need be specifically addressed.

Disclosures

All Authors: No reported disclosures
1401. Real-World Effectiveness of Inactivated and Live Attenuated Influenza Vaccines in Children During Three Recent Seasons: 2016–2019
Authors: Bandell Allyn , Mallory Raburn , Ambrose Christopher S
Published: January 2021

Background

Given the substantial burden of influenza in the pediatric population, influenza vaccination with live attenuated influenza vaccines (LAIVs) and/or inactivated influenza vaccines (IIVs) is now recommended for children in an increasing number of countries. In recent seasons, the real-world effectiveness of influenza vaccines has varied substantially. In the 2013/14 and 2015/16 influenza seasons, LAIV demonstrated reduced vaccine effectiveness (VE) against A/H1N1 strains. LAIV and IIVs have also demonstrated variable effectiveness against A/H3N2 strains in recent seasons. This study evaluated LAIV and IIV effectiveness in children between the 2016/17 and 2018/19 seasons.

Methods

Quadrivalent LAIV (LAIV4) and IIV effectiveness studies conducted in the pediatric population from 2016/17 through 2018/19 were identified from published literature, congress presentations, public health websites and personal communication with national investigators. Studies were excluded if they were from countries where Ann Arbor-backbone LAIV was not available for at least one season during the study period, were from randomized, interventional studies, or contained duplicate data from other publications.

Results

For the three seasons, point estimates of all-strain VE for children ranged from 20% to 74% for LAIV4 and from –20% to 68% for IIV (Fig 1A). During the same period, VE against A/H3N2 for children ranged from –76% to 74% for LAIV4 and from 3% to 56% for IIV (Fig 1B). Point estimates of VE against A/H1N1 for children were 50% and 90% for LAIV4 and ranged from 24% to 87% for IIV (Fig 1C). For influenza B, VE for children ranged from 31% to 80% for LAIV4 and from –12% to 80% for IIV (Fig 1D). Statistical comparison of LAIV4 and IIV VE across each season was not feasible due to the multivariate nature of each study cohort.

Figure 1. 2016–2019 Effectiveness of Inactivated and Live Attenuated Influenza Vaccines by Influenza Strain in Children

Conclusion

During three recent seasons, LAIV4 and IIV showed similar moderate effectiveness against all influenza strains, A/H1N1 strains, and B strains. VE against A/H3N2 for LAIV4 and IIV was good in 2016/17, but decreased in the 2017/18 and 2018/19 seasons. VE estimates for LAIV4 and IIV overlapped for all strains and each subtype, demonstrating the general comparability of LAIV4 and IIV VE in the seasons between 2016 and 2019.

Disclosures

Allyn Bandell, PharmD, AstraZeneca (Employee, Shareholder) Raburn Mallory, MD, AstraZeneca (Employee, Shareholder) Christopher S. Ambrose, MD, MBA, AstraZeneca (Employee, Shareholder)
1405. Clinical and laboratory features of fatal dengue fever in children: a case-control study
Authors: Freire Dolores E , Olaya Jeniffer D , Hawkes Michael
Published: January 2021

Background

Dengue fever (DF) is a mosquito-borne illness that causes significant morbidity and mortality in tropical climates. This study compared the clinical features of fatal DF cases to severe non-fatal, and non-severe controls in Ecuador.

Methods

Retrospective case-control study of children (1 month to 15 years) hospitalized with serologically-confirmed DF in Guayaquil, Ecuador from 2013 to 2017. Cases of severe, fatal (SF) DF were compared to two control groups: (1) severe DF survivors (SS); and (2) patients with dengue with warning signs (DWS), matched 3:1 to cases for age, sex, and admission date.

Observational trial profile

Results

1051 patients were admitted with suspected DF and 552 were IgM-positive. Patients were classified as SF (n=11), SS (n=30), or DWS (n=511) (Figure1). Among SF cases, median age was 9.6 years (IQR 5.5-11), 7 (64%) were male, and median time to death was 1.5 days (IQR 0.8-4.0). (Table 1) SF cases had a median of 3 (Range 0-5) encounters with healthcare providers prior to presentation, compared to 2 (Range 0-5, p=0.02) for SS and 2 (Range 0-3, p=0.02) for DWS. Physical findings more common in SF cases than controls included: higher weight, tachycardia, tachypnea, delayed capillary refill, and hepatomegaly (p< 0.05 for all comparisons). Neurological manifestations were more prevalent in the SF group: 9/11 (82%) patients compared to 15/30 (50%, p=0.09) in SS and 7/33 (21%, p< 0.01) in DWS. Total leukocyte count (7.8x103/µL versus 4.5x103/µL, p=0.03) and absolute neutrophil count (5.1x103/µL versus 2.1x103/µL, p=0.03) were higher in SF cases than DWS controls. Fewer SF patients received intravenous dextrose than SS controls (27% versus 70%, p=0.03) (Table 2).

Admission characteristics of children with dengue fever

Management and outcome

Conclusion

Delayed recognition by healthcare workers, higher weight, vital sign abnormalities, hepatomegaly, neurological symptoms, leukocytosis, neutrophilia, and lack of dextrose in intravenous solutions were associated with mortality in children with DF. These findings have implications for optimizing the diagnosis and management of severe pediatric dengue infection.

Disclosures

All Authors: No reported disclosures
1407. Cytomegalovirus (CMV) infection in the first year of life in a cohort of infants in rural Guatemala
Authors: Munoz Flor M , Lamb Molly , Waggoner Jesse , Paniagua-avila alejandra , Bauer Desiree , Connery Amy , Olson Daniel , Natrajan Muktha , Anderson evan , Calvimontes Mirella , Bolanos Guillermo , El Sahly Hana , Asturias Edwin J
Published: January 2021

Background

Little is known about the epidemiology of Cytomegalovirus (CMV) infection in low resource countries. We evaluated the frequency and effects of post-natal CMV infection in infants from a prospective cohort study designed to assess the effects of post-natal Zika on neurodevelopment (ND) in rural Guatemala.

Infants with CMV infection (blue bars) were older compared CMV-negative (red bars) infants.

Methods

Infants were evaluated for CMV infection by PCR using urine samples collected at 0-3 months of age. ND testing was conducted by local psychologists using a culturally adapted Mullen Scales of Early Learning (MSEL). We explored associations between CMV infection and microcephaly, neurological, visual and hearing deficits, malnutrition and ND outcomes at 1 year of age.

Results

The infant cohort (N = 469) had a mean age at enrollment of 1.5 (SD 0.75) months; 47% were female and 71% were breastfeeding at 1 year. A total of 103 (22%) were CMV positive and the majority of these (97%) were > 4 weeks of age at testing. Infants > 4 weeks of age were more likely to be CMV positive (P < 0.0001) (Figure). Gender was not correlated with CMV positivity. Among children with head circumference (HC) measurements, microcephaly (HC < 2 SD) was present in 9/87 (10.3%) CMV positive and 35/338 (10.4%) CMV negative infants at 0-3 months of age (p =0.99). Among 438 infants who underwent screening for hearing deficits and a complete ophthalmologic evaluation, none of the CMV positive children had abnormal vision or hearing. Abnormal neurological exams in the first year of life occurred in 50/100 (50%) CMV positive and 166/365 (45.5%) CMV negative infants (p =0.56). There was no association between CMV infection at 0-3 months and MSEL overall or subdomain scores at 1 year (overall Relative risk (RR) 1.02, 95% CI 0.99-1.05, p=0.16). Malnutrition at 0-3 months (RR: 1.53, 95% CI 0.89-2.66, p = 0.13) and 1 year (RR: 1.10, 95% CI 0.77-1.58, p=0.59) was not associated with CMV infection at 0-3 months.

Conclusion

In a cohort of Guatemalan infants, postnatal CMV infection was common (22%) and more likely to occur after the neonatal period. There was no correlation between CMV infection and microcephaly at 0-3 months or at 1 year of age, nor with abnormal nutritional, neurologic, ophthalmologic, hearing or ND deficits at 1 year of age. This is the first epidemiologic report on CMV infection in early life in rural Guatemala.

Disclosures

Molly Lamb, PhD, BioFire (Grant/Research Support)
1411. Risks and Outcomes of Adenovirus Disease in Pediatric HSCT Recipients –Comparison of Current Antiviral Treatment Options
Authors: Thomas Sanya J , Young Rebecca R , Steinbach William , Lugo Debra J
Published: January 2021

Background

Adenovirus can cause multi-organ dysfunction in hematopoietic stem cell transplant recipients (SCTr). It accounts for 22% of infection-associated mortality in umbilical cord transplant recipients (UCTr). This study determines whether transplant characteristics are associated with risk of adenovirus disease (ADVd), and compares time to resolution of ADVd between patients who received antiviral therapy.

Methods

We conducted a retrospective single center cohort study of pediatric patients undergoing stem cell transplant at Duke University between 2005 and 2016. We identified cases of single end-organ and disseminated ADVd (2 or more organs) using a classification tool defined a priori. We used a Cox proportional hazards (CPH) regression model to compare the hazard of ADVd between SCTr differing by type of transplant and type of conditioning regimen. We also used CPH to compare the hazard of time to resolution of ADVd between SCTr differing by absence or presence of antiviral therapy (cidofovir, brincidofovir or both).

Results

There are 830 subjects, including 93 subjects with ADVd post-SCT. UCTr had 3.30 times the hazard of developing ADVd compared to non-cord blood allogeneic transplants and 7.30 times the hazard compared to autologous transplants (Figure 1). No difference in hazard of ADVd was detected between patients who received myeloablative vs non-myeloablative conditioning. Twenty-seven percent of the subjects received antiviral therapy; these patients had higher mortality (38%). The majority (87%) of diseased subjects had resolution of disease. Subjects that did not receive antiviral therapy experienced earlier resolution of ADVd compared to subjects who received antiviral therapy even after adjusting for subjects with disseminated disease (HR (95% CI): 3.75 (1.57, 8.93), p=0.003). Subjects with single end organ disease had earlier resolution of ADVd compared to disseminated disease (HR (95% CI): 2.24 (1.22, 4.10), p=0.009).

Figure 1a. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of transplant.

Figure 1b. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of conditioning regimen.

Conclusion

This is the first pediatric cohort study to report risk factors and clinical outcomes of ADVd, irrespective of ADV-DNAemia. UCTr recipients have a higher hazard of ADVd compared to other SCTr. Contrary to previous reports studying ADV-DNAemia, our study noted an earlier resolution of ADVd in the absence of antiviral therapy.

Disclosures

All Authors: No reported disclosures
1417. Clinical Features and Outcomes of raoultella terrigena Infections. A Single-Center Experience from Karachi, Pakistan
Authors: Ahmed Ishfaque , Nasir Nosheen , Ali Bushra Jamil , Mahmood Syed Faisal
Published: January 2021

Background

Raoultella terrigena (formerly Klebsiella terrigena) is an environmental gram-negative rod, occasionally causing infections in humans, especially in elderly, immunosuppressed patients. Moreover, this organism tends to be multi-drug resistant, limiting treatment options. Evidence on clinical presentation and outcomes of this infection is limited; we conducted a cross-sectional study to get a better insight into these infections.

Methods

We conducted a cross-sectional study on all adult patients with clinical specimen positive for Raoultella terrigena at a 700-bedded tertiary care hospital in Karachi, Pakistan, between January 2013 to December 2018.

Results

A total of 58 patients with R. terrigena were identified. The median age was 61.5 years, and the male to female ratio was (60.9% vs. 39.1%). The most common site of infection was respiratory tract 28.3%, followed by urinary tract infections 26%, and central line-associated infections 15.2%. In 12 patients 22.6%, R. terrigena was a colonizer. Amongst infected cases, 23.6% were in shock, and of which 18.1% required vasopressors. 29.2% had respiratory failure requiring non-invasive ventilation in 13.9%, and mechanical ventilation in 15.3%. The previous history of multidrug-resistant organisms was present in 67.4% cases and the history of prior antibiotics use within the last six months was present in 78.3%. 91.3% of isolates were resistant to piperacillin-tazobactam and meropenem, 65.2% were resistant to colistimethate. However, tigecycline susceptibility maintained in 30.4% checked in n=31, 67.4% and fosfomycin sensitivity in 15.2% cases, checked in n=29, 63% cases. Eight patients lost to follow up. Majority of patients were treated with combination therapy n=31, 81.6% and meropenem plus colistemethate was the most commonly used combination n=11, 44%. The overall mortality rate was 44.7%. Among all recorded co-morbid conditions, chronic kidney disease was strongly associated with mortality (p= .029), as also the use of vasopressors (p= .005).Persons who had high (greater or equal to three) Charlson comorbidity index had high mortality (p=0.002).

Conclusion

R.terrigena is a highly drug-resistant organism with high mortality rate, and causes hospital-acquired respiratory tract infections in majority of patients.

Disclosures

All Authors: No reported disclosures
115. Influence of Antimicrobial Stewardship and Molecular Rapid Diagnostic Test on Antimicrobial Prescribing for Extended-spectrum Beta-lactamase and Carbapenemase-producing Bacteria in Bloodstream Infections
Authors: Coyne Ashlan Kunz , Casapao Anthony , Isache Carmen , Morales James , McCarter Yvette , Jankowski Christopher
Published: January 2021

Background

Molecular rapid diagnostic tests (mRDT) may help expedite the time to optimal antimicrobial therapy (TTOT) for extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing bacteria in bloodstream infections (BSI). The greatest impact of mRDT appears to occur when combined with antimicrobial stewardship program (ASP) intervention. The purpose of this study was to evaluate if mRDT + ASP influences the TTOT for patients with ESBL- and carbapenemase-producing E. coli and K. pneumoniae in BSI compared to conventional microbiological methods with ASP (CONV + ASP).

Methods

Multicenter, retrospective, cohort study evaluating five years of patients that had a positive E. coli or K. pneumoniae blood culture determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Patients were excluded if they had polymicrobial BSI, transferred–in with previously identified positive blood cultures, were immunosuppressed, or died before culture results.

Primary outcome was TTOT defined as time from blood culture draw to start of carbapenem therapy for ESBL-producing BSI and ceftazidime-avibactam, meropenem-vaborbactam, or at least one drug active in-vitro with the most-narrow spectrum for carbapenemase-producing BSI. Secondary outcomes were time to microbial clearance (TTMC) defined as the time from index blood culture draw to the time of first negative blood culture or hospital discharge, all-cause hospital mortality, 30-, 60- and 90-day readmission rates, and Clostridioides difficile rates.

Results

A total of 378 patients were included for analysis. Baseline characteristics were balanced between mRDT + ASP (n=164) and CONV + ASP (n=214). Infectious diseases consults were significantly greater for CONV + ASP compared to mRDT + ASP (82.2% vs 34.8%; p< 0.001). The mRDT + ASP demonstrated a statistically significant decrease in TTOT (20.5 hrs [(IQR 17.0–42.2 hrs)] vs 50.1 hrs [(IQR 27.6–77.9 hrs)]; p< 0.001) and TTMC (71.9 hrs [(IQR 54.1–108.5 hrs)] vs 91.2 hrs [(IQR 64.6–134.3 hrs)]; p=0.007). Other secondary endpoints were similar between groups.

Table 1. Comparison of baseline characteristics for the mRDT+ASP and CONV+ASP groups

Graph 1. Kaplan Meier time to optimal antimicrobial therapy

Graph 2. Kaplan Meier time to microbial clearance

Conclusion

Our study supports the additional benefit of mRDT to ASP on shortening the TTOT and TTMC in patients with ESBL- or carbapenemase-producing E. coli and K. pneumoniae in BSI compared to CONV + ASP.

Disclosures

All Authors: No reported disclosures
1420. A One Health Approach Examining the Potential Linkage between Agricultural Livestock and Human Antibiotic Resistance at the Watershed Level
Authors: Donner Linsey M , Li Xu , Snow Daniel D , Sangster Jodi L , Staley Zachery R , Amandus Loralee J , Mathews Wayne A , Bartelt-Hunt Shannon
Published: January 2021

Background

Antibiotic resistance is a significant public health threat and widespread use of antibiotics in agriculture is increasing the concern about agricultural contributions to the dissemination of antibiotic resistant bacteria. Of concern is the level of exposure to antibiotics and antibiotic-resistant bacteria in the watershed. Consequently, adopting a One Health approach to measure antibiotic levels and identify antibiotic resistance gene (ARG) transfer at the human, animal and environmental interfaces is essential to better understand how antibiotic resistance is spread.

Methods

In this project, antibiotic levels were measured using passive organic chemical integrative samplers (POCIS) for 30-day periods from August – November 2018 from Elkhorn River and Shell Creek watersheds in Nebraska (Figure 1). In addition, whole genome sequences of bacterial isolates cultured from the watersheds were assessed to identify ARGs present on mobile genetic elements (MGE) that had >95% similarity to mobile ARG present in isolates recorded in the NCBI GenBank database was identified using ResFinder.

Figure 1. Sampling locations within the two watersheds.

Results

The study demonstrated significant antibiotic levels present throughout the watershed, with five of them associated with human usage (Table 1). In addition, seasonally based drug-resistant bacterial species was associated with specific antibiotic levels in the watershed (Figure 2). Mobile ARGs were detected in 87.5% of isolates collected from the Elkhorn River and 80.0% within Shell Creek (Figure 3).

Table 1. Pharmaceutical levels in the watershed

Figure 2. Antibiotic levels and drug-resistant bacteria in the watershed

Figure 3. Antibiotic resistance observed from each isolate at every sampling date and site. A colored bar denotes that resistance to that antibiotic was observed.

Conclusion

These results present evidence of transfer of highly mobile ARGs between environment, clinical, and animal-associated bacteria and highlight the need for a One Health perspective in assessing the spread of antibiotic resistance. The presence of significant levels of antibiotics persisting in this agricultural watershed points out the need for ongoing monitoring of compliance with the Food and Drug Administration (FDA) recommendation of veterinarian oversight of the use of antibiotics in the use of veterinary feed directive applications.

Disclosures

All Authors: No reported disclosures
1421. Assessing Serious Infections Common in Persons Who Inject Drugs in the United States and Tennessee
Authors: Lowry Michael , Fiske Christina , Rebeiro Peter F
Published: January 2021

Background

The opioid crisis is a public health emergency in the United States (US) and Tennessee (TN), and injection drug use predisposes users to a variety of serious infections. We therefore examined infection rates among persons who inject drugs (PWID) from 2001-2014 in the US and TN.

Methods

We conducted an ecological study using publicly available data including discharge diagnosis codes: the Healthcare Cost and Utilization Project (HCUP). We identified all persons from 2001-2014 with ICD-9 codes for bacterial infections common among PWID: endocarditis (IE), osteomyelitis (OM), septic arthritis (SpA), and skin/soft tissue infections (SSTI). We calculated rates of substance use and infection among all hospital discharges. Spearman’s rank correlation quantified the relationship between infection and reported hepatitis C seropositivity (HCV), Substance Abuse (SA) and opioid use disorder (OUD) rates. Poisson regression yielded incidence rate ratios (IRR) and 95% confidence intervals [-], and restricted cubic splines were fit to assess annual trends flexibly.

Results

Unadjusted rates of both substance use and infection among those discharged from hospitals were higher in the US overall than in TN from 2001-2014 (p< 0.05) (Figure 2,3). Overall infections, HCV (IRR=1.14 [1.12-1.17]), SSTI, OM, and SpA increased annually in the US; overall infections, HCV (IRR=1.14 [1.10-1.15]), and SSTI increased in TN. OUD (IRR=0.96 [0.94-0.98]) and IE (IRR=0.97 [0.97-0.98]) decreased in the US (Table 1). In the US, there were strong positive correlations between any other infection and HCV (ρ=0.87), IE and OUD (ρ=0.7), SSTI and HCV (ρ=0.9), OM and HCV (ρ=0.69), and SpA and HCV (ρ=0.68); IE was negatively correlated with HCV (ρ=-0.84). In TN, overall infections (ρ=0.68), and specifically SSTI (ρ=0.62), were correlated with HCV (Figure 1).

Table 1

Figure 1

Figure 2

Conclusion

Serious infections common in PWID are increasing in TN and the US; they correlate with HCV rates, which have risen significantly in hospitalized patients. Interestingly, opioid use disorder incidence from discharge data declined from 2001-2014 for both TN and the US, which may be due to coding lapses or shifts in type of opioid use with no well-known billing code. However, we must continue monitoring and mitigating both substance use and its sequelae.

Disclosures

All Authors: No reported disclosures
1422. Burden of Pertussis in South Korea: Implications for adults
Authors: Mungall Bruce , Kim Hyungwoo , Oh Kyu-Bin
Published: January 2021

Background

There are a limited number of published studies on pertussis disease burden and epidemiology in South Korea, particularly those evaluating the impact in adults.

Methods

We conducted a systematic literature review on pertussis epidemiology and burden of disease in South Korea. The objective was to highlight evidence gaps which could help improve awareness about pertussis disease in adults in South Korea.

Results

Of 940 articles published between January 2000 to December 2019, 19 articles provided data for pertussis epidemiology and 9 provided data in adults. Laboratory confirmation rates in adults varied according to methodology, likely influenced by study/sampling variations. Three studies reported serological evidence of infection in adolescents and adults (33-57%). Among cases, the average cough duration was 16.5 days (range 7-30 days) and over 85% of cases presented with paroxysmal cough, while only 25% of cases or less presented with a characteristic whoop or post-tussive vomiting. Importantly, in 4 studies reporting vaccination status, almost all adult cases had no history of pertussis vaccination since childhood.

Conclusion

Primary childhood vaccination rates in South Korea are among the highest globally, while adult pertussis vaccine uptake appears to be quite low. Our literature review suggests that pertussis is underreported in adults, as evidenced by serology data demonstrating that tetanus antibody levels are low while pertussis toxin antibody levels are relatively high, suggesting continued circulation of community pertussis. These findings highlight the need for strategies such as maternal immunization and decennial revaccination of adults to address the changing epidemiology and waning immunity. Active pertussis testing/reporting and better utilization of adult vaccine registries is required to help provide robust data for vaccine decision-making at the national level. In the current COVID-19 environment, strategies that can reduce clinic or hospital visits will have substantial benefits to authorities managing rapid increases in health care resource utilization, and vaccine preventable diseases provide an easy and immediate target for achieving that goal.

Disclosures

Bruce Mungall, PhD, the GSK group of companies (Employee, Shareholder) Hyungwoo Kim, MD, MPH, the GSK group of companies (Employee) Kyu-Bin Oh, MD, the GSK group of companies (Employee, Shareholder)
1425. Impact of Social Determinants on Racial Differences in Carbapenem-Resistant Enterobacteriaceae Incidence, Atlanta, 2012-2018
Authors: Smith Gillian , Bower Chris W , Fridkin Scott , Jacob Jesse T
Published: January 2021

Background

Public health prioritizes addressing social determinants of health to promote health equity. We hypothesized that social determinants of health, including poverty, are associated with racial disparity in the incidence of carbapenem-resistant Enterobacteriaceae (CRE).

Methods

The Georgia Emerging Infections Program conducted CDC-funded, active population-based CRE surveillance in metropolitan Atlanta (2017 population: 3.9 million) from 2012-2018. CRE cases were defined as Atlanta residents with a urine or normally sterile specimen growing E. coli, Klebsiella spp., or Enterobacter spp. resistant to ≥ 1 carbapenems (excluding ertapenem) and all third generation cephalosporins tested. Poverty, education and insurance levels by census tract of residence were obtained from the US Census Bureau’s 2017 American Community Survey. Race and end-stage renal disease (ESRD) were determined from chart review, and primary care provider (PCP) shortage area was obtained from the Health Resources and Services Administration. Age-adjusted incidence rate ratios were individually calculated using direct age standardization. Covariates were considered for inclusion in a multivariable Poisson regression model for the expected rate of CRE.

Results

Adjusting for age, CRE incidence was three times higher in blacks than whites. Higher CRE incidence was also observed among cases assigned > 40% below poverty level, > 15% below high school education, > 10% uninsured, and in a PCP shortage area (Table 1). CRE incidence was 58 times higher among ESRD cases than non-ESRD cases. In the multivariable model (Figure 1) addition of education, poverty or ESRD (p< 0.001), but not PCP access (p = 0.61) and insurance status (p=0.19), significantly reduced the racial difference in CRE incidence compared to race and age alone. Although controlling for age and either education, poverty level or ESRD reduced CRE among blacks, CRE incidence in blacks remained double that of whites.

Figure 1. Comparison of race CRE incidence rate ratio adjusting for age alone (red line) to adjusting for age and individual social determinants (blue bars)”

Table 1. Social Determinants Distribution and Age-Adjusted CRE Incidence Rate Ratio (N = 378)

Conclusion

Poverty level, ESRD and education only partially account for the racial differences seen in CRE incidence. While ESRD suggests a possible biologic component, persistent racial differences indicate the need for targeted public health interventions to address social determinants of health.

Disclosures

All Authors: No reported disclosures
1426. Increased Visits to Respiratory Protection Webpages during COVID-19
Authors: Lybrand Evan , Micciche Mary , Tienken Burton , Cichowicz Jaclyn , Fries Marisa , Senk Mark , Casey Megan
Published: January 2021

Background

COVID-19 transmission is thought to occur mainly via respiratory droplets produced when an infected person coughs or sneezes. Respiratory protection devices, when properly fitted and used, can prevent this type of illness transmission.

Methods

The Centers for Disease Control and Prevention’s National Personal Protective Technology Laboratory (NPPTL) within the National Institute of Occupational Safety and Health (NIOSH) is responsible for the certification and approval of respirators for use in occupational settings. NPPTL maintains webpages with information on respiratory protection devices. We monitored the number of webpage views for several NPPTL webpages from January 1, 2020 to May 8, 2020. The number of webpage visits was then compared to significant events during the COVID-19 outbreak as well as the previous year’s webpage visits.

Results

The landing page for NIOSH-approved N95 respirators received the most visits. This page received a total of 1,637,250 webpage visits with a peak of 63,715 on February 26, 2020, a 38,989% increase from the average daily page visits for that same month in 2019. This occurred on the same day as the White House gave its first televised briefing on COVID-19. The page providing general information on filtering facepiece respirators, including N95 respirators received 834,186 webpage visits with a peak of 20,520 on April 3, 2020, a 13,659% increase from the average daily webpage visits for that same month in 2019. This occurred on the same date as new CDC recommendations were provided for using cloth face masks in public places. The counterfeit respirator page maintained a steady, but small number of webpage visits, but increased from 4,261 on March 27, 2020 to 68,145 on March 29, 2020. This occurred as the first reports of fraudulent respirators were being published in the media. It then fell to 18,562 on March 30, 2020 and 13,093 on March 31, 2020. While most webpage visits were from the United States, visits from China, and Canada were higher than previous years.

Conclusion

During COVID-19 there was a large increase in the number of webpage visits for respiratory protection information which coincided with major events and media reports. Accurate, accessible respiratory protection information is an important resource during public health emergencies.

Disclosures

All Authors: No reported disclosures
1428. Lyme Disease Treatment in the United States: Prescribing Patterns from a Nationwide Commercial Insurance Database, 2016-2018
Authors: Beeson Amy M , Marx Grace E , Schwartz Amy M , Hinckley Alison F
Published: January 2021

Background

Lyme disease (LD) is the most common vector-borne disease in the United States and is a significant public health problem. The use of non-standard antibiotic treatment regimens for LD has been associated with adverse effects; however, the overall landscape of treatment has not been described previously. We aimed to describe real-world antibiotic prescribing patterns for LD.

Methods

We performed a retrospective analysis of the MarketScan commercial claims database of outpatient encounters from 2016-2018 in the United States. We identified all individuals with a visit that included an LD diagnosis code and a prescription within 30 days of the visit for one or more of 12 antibiotics that may be prescribed for LD. We then categorized each individual as having received either standard or non-standard treatment during the two-year period. Standard treatment was defined as treatment with a first, second or third-line antibiotic for LD, for no longer than 30 days, and for no more than two episodes during the study period. Descriptive and multivariable analyses were performed to compare characteristics of people who received standard vs non-standard treatment for LD.

Results

A total of 84,769 prescriptions met criteria for inclusion, written for 45,926 unique patients. The mean duration of prescriptions was 21.4 days (SD 10.8). Most individuals (84.5%) treated for LD received standard treatment during the study period. Female gender (OR 1.5, p< 0.0001) and age 19-45 (p=0.0003) were significantly associated with being prescribed non-standard LD treatment. Treatment in low-incidence states (OR 2.2 compared to high-incidence states, p< 0.0001) and during non-summer months (OR 2.2, p< 0.0001) was more likely to be non-standard.

Age distribution of patients receiving treatment for Lyme disease, by gender and age at first prescription

Seasonality of standard versus non-standard treatment of Lyme disease

Conclusion

In this population of employed, young, and insured patients, young and middle-aged women were at the highest risk of receiving non-standard LD treatment. Treatments prescribed in states with low incidence of LD or during non-summer months were also more likely to be non-standard, a trend which likely reflects misdiagnosis or overtreatment of LD. Future studies are needed to further define prescriber and patient factors associated with non-standard LD treatment and related adverse outcomes.

Disclosures

All Authors: No reported disclosures