bluuebunny/crossref_metadata_2025_split huggingface dataset:
1456. Resistance Mechanisms of Tigecycline in Enterococcus faecalis
Authors: Bai Bing , Wen Zewen , Lin Zhiwei , H Tam Vincent , Yu Zhijian 
Published: January 2021

Abstract

Background
Enterococcus faecalis have been regarded as one of the leading causes of the nosocomial infections worldwide. Tigecycline (TGC) is considered as a choice of last resort for the treatment of infections caused by multidrug-resistant E. faecalis, however, the emergence of TGC non-susceptibility has posted the therapeutic challenge. Non-susceptibility in clinical strains could be due to resistance (MIC &gt;0.5 mg/l) or heteroresistance. Therefore, this study aimed to understand the underlying molecular mechanisms of TGC resistance and heteroresistance in E. faecalis.

Methods
In vitro induction experiments were carried out under TGC pressure with two TGC- sensitive E. faecalis strains. Heteroresistance was evaluated by population analysis profiling (PAP) in 270 clinical TGC- sensitive E. faecalis strains. TGC susceptibility was determined by the agar dilution method. Resistance and heteroresistance mechanisms were investigated by identifying genetic mutations in tetracycline (Tet) target sites and susceptibility testing in the presence of the efflux protein inhibitors phenylalanine-arginine-β-naphthylamide (PaβN) and carbonyl cyanide m chlorophenylhydrazine (CCCP). Comparison of single nucleotide polymorphism in the whole genome between the parental isolate and two TGC-resistant strains were investigated by next-generation sequencing.

Results
No mutations in Tet target sites in seven TGC heteroresistant strains were present, whereas the mutations in Tet target sites of seven TGC-resistant E. faecalis were frequently found (Table 1). TGC MICs in heteroresistant strains were reduced by CCCP (Table 2). Whole genome sequencing revealed the same non-synonymous mutations and transcoding deletions in the exons of several genes encoding for various enzymes or transfer systems (Table 3).
Table 1. The characteristics of the antimicrobial susceptibility, resistance mechanism of TGC-induced resistant isolates

Table 2. Characteristics of clinical heteroresistant mother E. faecalis strains and heteroresistance-derived E. faecalis clones

Table 3. List of mutation-related genes, amino acids and proteins by comparison of whole genome between the parental isolate and the TGC-induced resistant strains

Conclusion
Our data indicated that the main mechanism of TGC heteroresistance in E. faecalis might be associated with the efflux pumps. TGC resistance in E. faecalis was associated with mutations in the 16SrRNA site or 30S ribosome protein S10. The genetic mutations in several enzymes and transfer systems might also participate in the resistance development to TGC in E. faecalis.

Disclosures
All Authors: No reported disclosures
1457. Serial Passage of Enterobacteriaceae to Explore Development of Carbapenem Resistance
Authors: Nissim Yosef , Slain Douglas , LaSala P Rocco 
Published: January 2021

Abstract

Background
Carbapenems are broad-spectrum antibacterials that have seen increased usage for the Enterobacteriales family in recent years. While carbapenem usage has been associated with increased antibacterial resistance, there is currently a lack of data comparing the risk of reduced susceptibility selection by the two most commonly used carbapenems in the US, ertapenem (ERT) and meropenem (MER). We conducted a novel serial passage experiment with clinical isolates of Enterobacteriales to assess the impact of repeated exposure to ERT or MER on phenotypic susceptibility patterns.

Methods
Non-duplicate clinical Enterobacteriales isolates were selected randomly for inclusion. Antimicrobial susceptibility testing was performed by CLSI disc diffusion methods. Standardized suspensions of isolates were plated on Mueller-Hinton agar, and ERT (10mcg) and MER (10mcg) discs applied. Zones of inhibition were measured and recorded after 16-18 hours incubation. Growth from the innermost zone of inhibition around each disc was used to prepare subsequent suspensions for serial susceptibility testing. This process would be repeated daily for 10 days. Each subsequent serially-passaged isolated was tested against both ERT and MER. Daily zones of inhibition were measured and interpreted. Baseline & final susceptibilities were determined by automated methods (Vitek 2).

Results
Seventeen Enterobacteriaceae isolates were selected, including: Klebsiella pneumoniae (n=11), Klebsiella oxytoca (n=2), Escherichia coli (n=1), Morganella morganii (n=1), and Enterobacter cloacae (n=2). Despite a greater degree of reductions in zones of inhibition with repeated ERT exposure (vs MER), the overall 10 day trends were not found to be significant different (P=0.529). Resistance developed to ERT in six isolates compared to one MER-resistant isolate (P = 0.053). E. cloacae was the only species to show a significant change between drugs (P=0.010). Two of three isolates that developed reduced zone changes &gt; 10mm to MER were initially exposed to ERT on an earlier plate.

Conclusion
This novel experiment identified the development of some nonsignificant reductions in susceptibility with ERT after serial exposure. Results from this pilot study should encourage larger well-designed studies in this area.

Disclosures
All Authors: No reported disclosures
1461. Impact of the Ampicillin/Sulbactam Shortage on Antibiotic Prescribing and Clinical Outcomes for Adult Inpatients with Aspiration Pneumonia
Authors: Staicu Mary L , Murphy Ian , Laguio-Vila Maryrose R 
Published: January 2021

Abstract

Background
Ampicillin/sulbactam is a recommended first-line agent for the treatment of aspiration pneumonia. Due to the ampicillin/sulbactam shortage, beginning in March 2019, alternative therapies, such as ceftriaxone plus metronidazole, have been utilized more frequently. The objective of this study is to examine clinical outcomes in adult inpatients treated with either ampicillin/sulbactam or ceftriaxone/metronidazole for aspiration pneumonia.

Methods
An electronic health record report identified patients ≥18 years of age that received ampicillin/sulbactam (pre-March 2019) or ceftriaxone/metronidazole (post-March 2019) with the indication of aspiration pneumonia. The primary objective was to describe 30-day all-cause readmission rates for patients that received ampicillin/sulbactam compared to ceftriaxone/metronidazole. The secondary objectives included hospital length of stay (LOS), 30-day all-cause mortality, C.difficile infection (CDI) within 3 months, and total antibiotic costs.

Results
A total of 86 patients (50 received ampicillin/sulbactam and 36 received ceftriaxone/ metronidazole) were included. Demographics were similar between groups. There was no significant difference in 30-day all-cause readmission rates (30% vs 19%, p=0.322). The ampicillin/sulbactam group, however, was found to have a significantly higher rate of 30-day all-cause mortality (12% vs 0%, p=0.038). Additionally, total duration of therapy was found to be significantly shorter in the ampicillin/sulbactam group (5 vs 7 days, p=0.002) with reduced overall cost of therapy($130 vs $235, p&lt; 0.001). No differences were observed in hospital LOS or CDI within 3 months.

Conclusion
No difference was observed in 30-day all-cause readmissions in patients receiving ampicillin/sulbactam compared to ceftriaxone/metronidazole for the treatment of aspiration pneumonia. Further analyses are recommended to evaluate the impact on 30-day all-cause mortality.

Disclosures
All Authors: No reported disclosures
1462. The protective effect of pneumococcal vaccination on cardiovascular disease in adults: A systematic review and meta-analysis
Authors: Marra Fawziah , Zhang Angel , Gillman Emma , Bessai Katherine , Parhar Kamalpreet , Vadlamudi Nirma Khatri 
Published: January 2021

Abstract

Background
Epidemiological studies suggest a link between pneumococcal infection and an adverse cardiovascular outcome such as myocardial infarction. Therefore, studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. We conducted a meta-analysis to summarize the available evidence on the impact of PPV23 on cardiovascular disease

Methods
A literature search from January 1946 to September 2019 was conducted in Embase, Medline and Cochrane. All studies evaluating PPV23 compared to a control (placebo, no vaccine or another vaccine) for any cardiovascular events including myocardial infarction (MI), heart failure, cerebrovascular events were included. Risk ratios (RRs) were pooled using random effects models.

Results
Eighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91;95% CI: 0.84-0.99), and MI (RR of 0.88; 95% CI:0.79-0.98) in all age groups, with a significant effect in those 65 years and older, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95%CI: 0.68-0.88), specifically in those aged 65 years and older (RR: 0.71; 95%CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination.

Conclusion
Polysaccharide pneumococcal vaccination decreases the risk of a cardiovascular event, specifically acute MI in the vaccinated population, particularly those 65 years of age and older. It would be highly beneficial to vaccinate the population who is at greater risk for cardiovascular diseases.

Disclosures
Fawziah Marra, BSc (Pharm), PharmD, Pfizer Inc (Research Grant or Support) Nirma Khatri Vadlamudi, BA, BS, MPH, Pfizer Inc (Research Grant or Support)
1464. Adjuvant Systemic Steroid Therapy and Length of Hospital Stay in Pneumonia Patients: A Retrospective Cohort Study in a Community Hospital
Authors: Mahatanan Rattanaporn 
Published: January 2021

Abstract

Background
Pneumonia is a leading cause of morbidity and mortality worldwide resulting in a substantial healthcare expenditure. Antimicrobial agents are the main treatment. Recent studies showed the benefits of steroid therapy as an adjuvant therapy for patients with pneumonia; however, the overall evidence is still controversial.

Methods
Electronic medical records of hospitalized patients (age &gt;18) at a community hospital in a rural Maine with the discharge diagnosis of pneumonia in 2015 and 2016 were reviewed. Demographics, comorbidities, physical examination, initial laboratory, and Pneumonia Severity Index (PSI) were collected for each patient. The exposure was a systemic steroid administered by either oral or intravenous. The outcomes included length of hospital stay (LOS), inpatient mortality, and transfer to tertiary care center. Competing-risks regression was utilized to examine the association between steroid and LOS. Multivariable logistic regression analysis adjusted for propensity score was used for other outcomes.

Results
A total of 414 patients were included. 277(63%) patients received systemic steroids. Overall, steroid use was significantly associated with shorter LOS (HR 1.26, 95%CI 1.03-1.54, p=0.02) and decrease inpatient mortality (OR 0.11, 95%CI 0.03-0.45, p&lt; 0.01). In subgroup analysis, steroid associated with shorter LOS only in patients with PSI class IV (HR 1.38, 95%CI 1.02-1.89, p=0.04) and PSI class V (HR 2.04, 95%CI 1.11-3.74, p=0.02). There was an association of steroid and shorter LOS in subgroup of COPD patients (HR 1.42, 95%CI 1.02-1.97, p=0.03).
Table 1: The baseline characteristics of hospitalized patients with a diagnosis of pneumonia who received steroid vs non-steroid

Figure 1: Subgroup analysis the effect of steroid and lenght of hospital stay (LOS)

Conclusion
Our study concluded that adjuvant steroid therapy associated with a decrease in length of hospital stay and improved inpatient mortality in hospitalized pneumonia patients. Steroid was most beneficial to those with severe pneumonia (PSI class IV-V) and COPD patients.

Disclosures
All Authors: No reported disclosures
1466. Antibiotic utilization reports may reduce prescribing practices for Upper Respiratory Infections
Authors: Salcedo David Augusto Terrero , Kelly Allison , Tate Victoria 
Published: January 2021

Abstract

Background
More than 90% of Upper respiratory tract infections (URI) have a viral etiology; nonetheless, these represent the most common reason for ambulatory antibiotic prescription. This translates in higher risk of antibiotic-related adverse events and promotion of antimicrobial resistance.

Methods
A prospective single-center intervention surveying and providing individual, face-to-face comparative reports of antibiotic utilization, for any of the 4 diagnostic entities that constitute upper respiratory tract infection (common cold, pharyngitis, acute rhinosinusitis and acute bronchitis), was performed in our Emergency Department.
Example of monthly provider reports used which included general and individualized goals.

Results
A total of 12 health care providers were followed for 12 months. Education, prescribing reports and individual goals were provided. The pre-intervention prescription rate from September to December 2018 averaged 74.75% (SD 20.59, 95% CI 61.6-87.8), with a post-intervention rate of 55.5% from September to December of 2019 (SD 19.20, 95% CI 43.3-67.7) that was statistically significant (p=0.0036). A higher use of antibiotic was observed in physicians when compared to non-physician providers in both pre and post intervention stages (reduction of 16.6% vs 23% after intervention respectively), with no statistical difference between the two groups (CI 95% of -38.82 to 2.395, p=0.0773). A proposed target of 50% or less was observed in 5 of 12 providers (41.6%), and 2 out of 12 (16.7%) had increase in their antibiotic utilization rate.
Comparative use of antimicrobials in the pre (September-December 2018) and post (September-December 2019) - intervention periods.

Average individual antimicrobial use rate before and after intervention.

Conclusion
Routine face-to-face utilization reports may constitute an effective approach in reducing antibiotic prescription practices in the Emergency Department, and potentially, in other outpatient healthcare settings.

Disclosures
All Authors: No reported disclosures
1475. Impact of a Routine Infant PCV Program on the Serotype Distribution of Episodes of Invasive Pneumococcal Disease (IPD) and Non-bacteremic Pneumococcal Pneumonia in Adults
Authors: McGeer Allison 
Published: January 2021

Abstract

Background
Herd immunity from pediatric pneumococcal conjugate vaccine (PCV) programs has resulted in substantial reductions in IPD due to PCV serotypes (ST). We assessed whether similar changes in ST distribution occur in non-bacteremic pneumococcal pneumonia (NBPP).

Methods
The Toronto Invasive Bacterial Diseases Network performs population-based surveillance for IPD and hospitalized, culture-confirmed NBPP in Toronto/Peel Region, Canada (Pop 4.5M). Patient data are collected by interview/chart review; illness associated with respiratory isolates is categorized using Musher criteria.

Results
Since 2002, 6627 episodes of IPD, and 7323 non-bacteremic episodes with a respiratory isolate of S. pneumoniae (2180 meeting modified Musher criteria for NBPP) have occurred in adults. Distributions of vaccine-type serotypes in IPD and NBPP pre-PCV7 (2002-2004), post-PCV7 (2006-2009) and late post-PCV13 (2014-2019) are shown in the Figure. There were no significant changes in distribution of vaccine serotype groups from 2014-2019 in IPD or NBPP. From 2014-2019, serotypes included in PCV13 and PCV20 were associated with 33% and 59% of IPD cases, and 29% and 49% of NBPP cases in adults..
Figure. distribution of serotype groups included in different pneumococcal vaccines in cases of IPD and non-bacteremic pneumonia

Conclusion
Eight years post routine infant PCV13 implementation, PCV13 type IPD and NBPP persists in adults. The distribution of vaccine-type strains is similar in IPD and NBPP; although non-vaccine-type strains are more common in NBPP.

Disclosures
Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)
1478. Impact of Short versus Long Treatment Durations for Respiratory Tract Infections Caused by Non-fermenting Gram-negative Bacilli in Lung Transplant Recipients
Authors: Derringer Jon , Anderson Eve , Hage Chadi , Desai Armisha 
Published: January 2021

Abstract

Background
In lung transplant recipients, respiratory tract infections are associated with faster progression through stages of bronchiolitis obliterans syndrome and mortality. Common causative pathogens for respiratory tract infections (RTIs) include non-fermenting gram-negative bacilli (NFGNB). Data to guide optimal treatment durations for NFGNB RTIs in this population are limited.

Methods
This was a single-center, retrospective, cohort study of adult lung transplant recipients who received systemic antibiotic treatment for RTIs caused by NFNGB and had at least 28 days of post-treatment follow-up. Analyses were conducted for each patient’s initial NFGNB RTI as well as all independent NFGNB RTIs episodes. Groups were divided into NFGNB RTIs treated for a short (≤ 10 days) versus long (&gt; 10 days) duration of effective antibiotic therapy. The primary outcome was the incidence of recurrent NFGNB RTIs within 28 days post-treatment. Recurrence was defined as isolation of the same organism in a respiratory culture requiring treatment with systemic antibiotics as determined by the prescribing physician.

Results
We included 207 lung transplant recipients with 334 NFGNB RTIs (n=129 short; n=205 long) from a period of January 1, 2010 to July 1, 2019. The most common causative pathogen was P. aeruginosa (77% and 82%) and most NFGNB RTIs were treated inpatient (60% and 53%) in both groups. The median duration of therapy was 10 days and 14 days for the short and long treatment durations, respectively. The primary outcome occurred in 14/129 (11%) of the NFGNB RTIs treated for ≤ 10 days and 28/205 (14%) of those treated for &gt; 10 days. No difference in recurrence within 28 days was detected in NFGNB RTIs treated for ≤ 10 days (aOR, 0.69; 95% CI, 0.34-1.4; p=0.149). Use of adjunctive inhaled antibiotics was associated with reduced recurrence (aOR, 0.38; 95% CI, 0.16-0.92; p=0.032).

Conclusion
In lung transplant recipients with NFGNB RTIs, no difference in infection recurrence was detected between treatment durations for ≤ 10 days compared to &gt; 10 days. Further investigation analyzing treatment durations for respiratory tract infections as well as the utility of adjunctive inhaled antibiotics are warranted in this patient population.

Disclosures
All Authors: No reported disclosures
1481. Incidence of Pertussis in Older Adults in England and the United Kingdom: A Large, Retrospective Database Analysis
Authors: Aris Emmanuel , Akpo Esse Ifebi , Bhavsar Amit , Harrington Lauriane , Merinopoulou Evie , Sawalhi-Leckenby Nicola , Turriani Elisa , Meszaros Kinga , Lambrelli Dimitra , Mukherjee Piyali 
Published: January 2021

Abstract

Background
Pertussis affects people of all ages and can lead to severe complications in adults, including hospitalization. Pertussis immunity, whether vaccine-induced or from natural infection, wanes over time. Therefore, despite extensive pediatric vaccination against pertussis, adults remain susceptible to the disease. Here we present the reported incidence of pertussis in people ≥ 50 years old (≥ 50yo) in England and the United Kingdom (UK).

Methods
We performed an observational, retrospective database analysis using the UK Clinical Practice Research Datalink GOLD and Aurum primary care databases, and Hospital Episode Statistics database when available for English subjects (HES-Eng), 2009-2018. Occurrence of pertussis was identified by diagnostic codes recorded in primary care only for the UK subset, and primary care and/or secondary care for HES-Eng.

Results
In the ≥ 50yo UK population, a total of 47.1 million (m) person-years of follow-up (PYFU) including 28.5m PYFU for HES-Eng, were included. In the UK, the pertussis Incidence Rate (IR) across all years was 5.44 per 100,000 PYFU. Yearly IRs ranged from 0.79 – 11.40 per 100,000 PYFU and reflected the cyclic epidemiology of pertussis. A peak of IR was observed in 2012, known to be an outbreak year, and observed IRs were higher in 2013-2018 (4.75 – 9.73 per 100,000 PYFU) than 2009-2011 (0.79 – 1.48 per 100,000 PYFU). In the HES-Eng population, overall IR was 5.76 per 100,000 PYFU. IRs were highest in the younger age groups (HES-Eng: 8.88 in 50-54 yo; 1.42 in ≥ 85 yo) (see table 1 and 2).
Table 1

Table 2

Conclusion
The observed reported IR of pertussis was similar in the UK and HES-Eng populations, noting the inclusion of secondary care diagnoses in the latter. The dynamics of IRs across years are consistent with estimated IRs from Public Health England data. Considering the burden of pertussis established elsewhere in older adults, and their non-negligible contribution to the whole population incidence, strategies for the prevention of pertussis should include this age group.

Disclosures
Emmanuel Aris, PhD, the GSK group of companies (Employee, Shareholder) Esse Ifebi Akpo, n/a, the GSK group of companies (Employee, Shareholder) Amit Bhavsar, MBBS, MHA, the GSK group of companies (Employee) Lauriane Harrington, n/a, the GSK group of companies (Employee) Evie Merinopoulou, MSc, Evidera Ltd (Employee)the GSK group of companies (Consultant) Nicola Sawalhi-Leckenby, MSc, Evidera Ltd (Employee)the GSK group of companies (Consultant) Elisa Turriani, PhD, the GSK group of companies (Employee) Kinga Meszaros, MBA, the GSK group of companies (Employee, Shareholder) Dimitra Lambrelli, PhD, MPharm, Evidera Ltd (Employee)the GSK group of companies (Consultant) Piyali Mukherjee, MBBS, MPH, the GSK group of companies (Employee, Shareholder)