bluuebunny/crossref_metadata_2025_split huggingface dataset:
165. Cefiderocol Treatment for Serious Infections Caused by Carbapenem-resistant Bacteria: Post-hoc Analysis of Outcomes by Pathogen in the CREDIBLE-CR Study
Authors: Matsunaga Yuko , Ariyasu Mari , Takemura Miki , Yamano Yoshinori , Toyoizumi Kiichiro , Kinoshita Masahiro , Echols Roger , Den Nagata Tsutae 
Published: January 2021

Abstract

Background
The efficacy and safety of cefiderocol (CFDC), a novel siderophore cephalosporin, for the treatment of serious infections due to carbapenem-resistant (CR) Gram-negative pathogens was assessed in the CREDIBLE-CR study. The current analysis evaluated clinical and microbiological outcomes by baseline CR pathogen.

Methods
An open-label, prospective, randomised 2:1, Phase 3 study (CREDIBLE-CR; NCT02714595) was conducted in adult patients with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, bloodstream infections or sepsis, and complicated urinary tract infections caused by CR Gram-negative pathogens. Patients received either intravenous (IV) CFDC 2g, q8h, 3-h infusion, or IV best available therapy (BAT: up to 3 drugs in combination), for 7–14 days (extendable to 21 days). Clinical and microbiological outcomes were assessed in the CR microbiological intent-to-treat (CR-MITT) population by CR pathogen, baseline MIC and by mechanism of carbapenem resistance at test of cure (TOC). Only summary statistics were collected.

Results
In the CR-MITT population (CFDC N=80; BAT N=38), Acinetobacter baumannii (46.3% and 44.7%), Klebsiella pneumoniae (33.8% and 31.5%), and Pseudomonas aeruginosa (15% and 26%) were the most frequent pathogens in CFDC and BAT arms, respectively. For all CR pathogens, clinical cure rates were achieved in 52.5% in the CFDC arm and 50.0% in the BAT arm at TOC; rates were similar between treatment arms by baseline CR pathogen (Table 1). Numerically higher clinical cure and microbiological outcomes were observed with CFDC for Enterobacterales (Table 1), especially against NDM-producing bacteria or those with porin-channel mutations (Table 1). CFDC MIC values ranged between ≤0.03 and 4 μg/mL, except for one pathogen (Table 2). Microbiological outcomes for CR A. baumannii, CR K. pneumoniae, and CR P. aeruginosa at TOC by baseline MICs of ≤4 μg/mL ranged between 0–40%, 0–100%, and 0–100%, respectively; at MIC ≤4 μg/mL, clinical and microbiological outcomes were equal (Table 2).

Conclusion
CFDC, via a novel mechanism of entry and its stability against β-lactamases, was effective against serious infections caused by CR pathogens with various resistance mechanisms or baseline MIC values.

Disclosures
Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee)
172. Serum Igg Profiling Healthy 1- and 2- year Old Toddlers Reveals a Subgroup with Clinically Informative Reactivities to Pathogens and Autoantigens
Authors: Reto Patricia Pichilingue , Raj Prithvi , Li Quan-Zhen , Dozmorov Igor , De la Morena Maria Teresa , vanOers Nicolai 
Published: January 2021

Abstract

Background
The antibody repertoire in an infant/toddler develops in response to the microbiome, infections, environmental exposures, and vaccinations. Monitoring the specificity of these antibody responses in normal toddlers will provide indicators of disease susceptibility.

Methods
The serum Immunoglobulin (Ig)G and IgM antibody reactivity patterns in 1- and 2-year-old healthy toddlers was determined by examining the Ig specificity to diverse infectious agents, autoantigens and vaccine antigens with an antigen array. The toddlers were stratified based on their antibody reactivity to these diverse antigens with a normalized fluorescence intensity measure. Repeat profiling was performed at year 2 to reveal longitudinal changes in the IgG and IgM responses. Clinical information, along with DNA sequencing, and selected cytokine assays were used to establish an odds ratio for immune disease potential among the cohort.

Results
Healthy 1- and 2- year old IgG responses revealed cohorts of low, moderate, and high Ig responder groups that was unconnected with total serum IgG levels. The high responder group had elevated IgG reactions to selected pathogens, particularly viruses as well as to autoantigens. This high reactivity group, representing 17% of the cohort, had high odds ratios with maternal gestational diabetes, age, and a family history of asthma. While all toddlers developed strong antibody responses to Measles-Mumps-Rubella vaccines (MMR), more variation was noted towards other vaccines. In infections to Molluscum contagiosum, the IgG serum levels were transient regardless of the responder group. The high responder group had DNA polymorphisms linked to enhanced immune responses that correlated with elevated cytokine levels as well as eczema and asthma.

A subset of toddlers has strong IgG responses to pathogens and vaccines

Conclusion
A subset of normal healthy toddlers has a high potential for immune system abnormalities and autoimmunity based on higher serum antibody responses to pathogens and autoantigens, genetic polymorphisms, and elevated cytokine responses.

Disclosures
All Authors: No reported disclosures
176. Selected Impact of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) on Invasive Pneumococcal Disease (IPD) at Eight Children’s Hospitals in the United States. 2014–2019
Authors: Kaplan Sheldon L , Barson William J , Lin Philana L , Romero Jose R , Bradley John S , Tan Tina Q , Pannaraj Pia S , Givner Larry , Hulten Kristina G 
Published: January 2021

Abstract

Background
The 2011 IDSA/PIDS Clinical Practice Guidelines for the Management of Community-acquired Pneumonia (CAP) in Children Older than 3 months recommended empiric treatment with either ampicillin/penicillin or ceftriaxone based on PCV13 vaccine status and the local antibiotic susceptibilities of IPD isolates. No study has addressed differences in antibiotic susceptibilities for isolates from children with pneumococcal pneumonia (PP) based on PCV13 status.

Methods
Investigators from 8 US children’s hospitals identified infants and children with IPD between 1/1/2014 and 12/31/2019. IPD was documented by positive cultures from a normally sterile site. PP diagnosis required an abnormal chest radiograph. Clinical data were recorded and isolates analyzed for serotype (ST) by the capsular swelling method and antimicrobial susceptibilities by standard methods. Administration of PCV7/13 was documented through the patient’s medical records, health care provider or a vaccine registry. Fisher Exact was performed; p&lt; 0.05 was significant.

Results
690 IPD patients with isolates were available (0–18 y); 24% (166/690) of the isolates were PCV13 STs (ST3-75, ST19F-45, ST19A-36, ST7F-5, other STs-5). The most common non-PCV13 ST isolates were ST35B-60, ST23B-59, ST33F-47, ST22F-43, ST15C-35, ST23A-27, ST15B-26, ST10A-26, ST15A-23. Of non-PCV13 isolates, 41% (217/524) were among the 7 additional STs in PCV20. For children with PP (n=157), the distributions of penicillin (Table) (p=0.8) and ceftriaxone MICs were no different for isolates obtained from children regardless of prior PCV13 doses. Less than 7% of PP isolates were resistant to penicillin (MIC &gt;2 µg/mL).
Table. Minimal inhibitory concentrations (MIC) of pneumococcal isolates related to the number of PCV13 doses each patient received prior to pneumococcal pneumonia (PP).
Number of PCV13 doses

Conclusion
PCV13 status should not modify empiric antibiotics for children with suspected pneumococcal CAP. 41% of non-PCV13 IPD isolates were among the 7 additional PCV20 STs.

Disclosures
Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support) Tina Q. Tan, MD, Pfizer (Grant/Research Support, Other Financial or Material Support, Chair, DMSB for PCV20 vaccine) Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member)
318. Deferring Amputation in Diabetic Foot Osteomyelitis: Doing more Harm than Good?
Authors: Zhou Shiwei , Schmidt Brian M , Henig Oryan , Kaye Keith S 
Published: January 2021

Abstract

Background
Diabetic foot osteomyelitis (DFO) is a leading cause of below knee amputation (BKA). Even when medical treatment is deemed unlikely to succeed, patients with DFO are often resistant to amputation.

Methods
An observational cohort analysis was done on patients with DFO at Michigan Medicine who were evaluated by podiatry and recommended BKA from Oct 2015 - Jun 2019. Primary outcome was mortality after BKA recommendation. Secondary outcomes were healing of affected limb, rate of BKA or above knee amputation (AKA) and total antibiotic days in the 6 months following. All intravenous antibiotics and oral courses of linezolid and fluoroquinolones were captured.

Results
Of 44 patients with DFO, 18 chose BKA, 26 chose medical management with wound care. Mean age of the cohort was 61, 68% male, 80% white with a median Charlson Comorbidity Index of 6 (IQR 4,7). The two groups were similar with regards to demographics and comorbid conditions. Those who chose medical management did so because their infection was non-life-threatening and they desired to avoid amputation.
One-year mortality was greater in patients who were medically managed compared to those who had BKA (23.1% vs 0%, OR 11.7, 95% CI 0.6–222.9). Considering only the 33 patients who were followed for at least 2 years, 2-year mortality was also greater in the medically managed group compared to the BKA group (38.5% vs 5.6%, OR 10.6, 95% CI 1.2–92.7, Figure 1). Fewer patients in the medical management group had complete healing of their wound/stump compared to the BKA group (46.2% vs 88.9%, OR 9.3, 95% CI 1.8–49.1). In the medically managed group, 18 (69%) patients went on to require BKA or AKA at a median of 76.5 days compared to 2 (11%) in the BKA group who required AKA at 1 and 11 days following recommendation. Median antibiotic days were significantly greater in the medically managed group compared to the BKA group (55 IQR 42,78 vs 17 IQR 10,37, p=0.0017).

Conclusion
In this cohort of DFO patients where BKA was recommended, medical management was associated with increased mortality, poor healing of the affected limb, and excess antibiotic exposure compared to BKA. These findings are particularly notable as case mix and severity of illness were similar between the two groups. This study can be used to inform providers and patients in cases where BKA is recommended.

Disclosures
All Authors: No reported disclosures
319. Distribution of Joint Involvement for Arbovirus-Associated Persistent Arthralgia May Help Distinguish Between Similar Diseases
Authors: Farahani Shayan , Kikyo Fumitaka , Cui Charley , Palacio Federico , Powers-Fletcher Margaret 
Published: January 2021

Abstract

Background
Imported cases of arbovirus infections associated with persistent arthralgia in travelers returning from endemic areas are often misdiagnosed due to overlapping clinical presentations and lack of widely available diagnostic testing. Identifying differences in joint involvement between arboviruses that cause persistent arthralgia may facilitate an earlier diagnosis. The purpose of this study was to determine if such distinct joint involvement has been reported in published literature for arbovirus-associated persistent arthralgia.

Methods
Chikungunya (CHIKV), Ross River Virus (RRV), Sindbis Virus (SINV) and Mayaro Virus (MAYV) were selected for their association with persistent arthralgia. Candidate manuscripts were identified using the PubMed database and search terms included virus names as well as terms associated with persistent arthralgia. Inclusion criteria consisted of 1) patient data on persistent arthralgia and 2) description of joint involvement. Joint involvement data was manually extracted and compared between viruses using a Fisher’s exact test. Pairwise post-hoc comparisons were then conducted using Fisher’s exact test and a Bonferroni correction was applied.

Results
Data from 1,833 patients were extracted from 57 manuscripts that met inclusion criteria (RRV = 194, SINV = 87, CHIKV = 1,526, MAYV = 26). Reported involvement of hands, wrists, elbows, shoulders, ankles and knees were recorded (Table 1). Distribution of joint involvement was then calculated for each virus (Figure 1). The difference in distribution of joint pain between the four arboviruses was statistically significant (P = 0.004). Comparisons revealed RRV and CHIKV are distinguishable from each other (P = 0.004).
Table 1. Reported Joint Involvement

Figure 1. Distribution of Joint Involvement

Conclusion
These findings suggest that differences in distribution in joint involvement may exist between patients with persistent arthralgia following arbovirus infection. Future studies aimed at more clearly elucidating these differences are warranted and may help develop a more rapid and accurate diagnostic algorithm that could improve patient care.

Disclosures
All Authors: No reported disclosures
321. Eleven-year Case Series of the Anatomy and Microbiology of Musculoskeletal Infections in People who Inject Drugs
Authors: Schade Meredith A , London Abby , Lin Dan 
Published: January 2021

Abstract

Background
Complex musculoskeletal infections(MSKI) can be seen in injection drug users. The objective of the study was to describe the anatomic location and microbial etiology of MSKI.

Methods
This is a single center, eleven-year case series of adult patients admitted with infection of the musculoskeletal system from January 1, 2008 to December 31, 2018. Diagnosis codes for MSKI were used. As there are no diagnosis codes that specifically identify injection drug use, ICD-9 and ICD-10 codes for related diagnoses were used. The codes included opioid use disorder, drug abuse, heroin use, drug overdose, cocaine use, and methamphetamine use.Charts were then carefully reviewed to determine if a MSKI related to IDU had occurred. Fisher’s exact test was used to calculate P values.

Results
A total of 849 individual medical records were identified. Eighty-six distinct episodes of infection were found in eighty-two patients. Most patients were white, non-Hispanic, male, 50 years of age or younger. Tobacco use disorder(87.8%) and hepatitis C(64.6%) were common. Mental health disorders were identified in one third. The axial skeleton was involved in 61.6% and the appendicular in 25.6%. Soft tissue infection alone was present in 9%. Bacterial infections predominated with Staphylococcus aureus most frequent(67.4%) followed by Pseudomonas aeruginosa (11.6%). Candida species were uncommon. All soft tissue infections were polymicrobial. Infections of the appendicular skeleton were managed with antibiotics and surgery whereas infections of the axial skeleton were more likely to receive antibiotics alone. Seventy two percent had successfully completed treatment at one year. The remainder had relapsed due to same infection, died or were lost to follow up.
Demographics of Study Population

Anatomy and Microbiology of MSKI in PWID and 1-year Treatment Outcomes

Anatomy and Microbiology of MSKI in PWID with Different Treatment Modalities

Conclusion
MSKI in PWID continue to be found in younger persons with relatively few comorbidities. The infections predominantly involve the axial skeleton and are caused most often by Staphylococcus aureus. Gram-negative infections also occur and are due to environmental bacteria. Spinal infections were managed medically whereas infections of peripheral joints were also managed with surgery. An unfortunate number had relapse of infection, died or were lost to follow-up at 1 year, demonstrating the challenges of managing MSKI in this unique population

Disclosures
All Authors: No reported disclosures
348. Etiology of Eosinophilic Meningitis in Korea
Authors: Park Sunghee , Jung Jiwon , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Kim Min Jae 
Published: January 2021

Abstract

Background
Eosinophilic meningitis is defined as the presence of more than 10 eosinophils per mm3 in the cerebrospinal fluid (CSF), or eosinophils accounting for more than 10 percent of CSF leukocytes in a patient with symptoms or signs suggestive of acute meningitis. Parasites are known to be the most common cause of eosinophilic meningitis worldwide, but there is limited research on patients in South Korea.

Methods
We retrospectively reviewed patients with eosinophilic meningitis at a tertiary hospital in Seoul, South Korea, from 2004 to 2018. Patients who were suspected of having a non-infectious cause were excluded. Etiology and clinical characteristics such as age, sex, risk factors, symptoms and signs, laboratory and radiologic findings, treatment, and prognosis were identified.

Results
Of the 35 patients included in this study, 11 (31.4%) had parasitic causes, with 8 (22.9%) diagnosed as neurocysticercosis, and 3 (8.6%) as toxocara meningitis. Four (11.4%) were diagnosed with fungal meningitis, and underlying immunodeficiency was found in 2 of these patients. Tuberculous meningitis was suspected in 4 (11.4%), while viral and bacterial meningitis were rare causes of eosinophilic meningitis, with 2 (5.7%) and 1 (2.9%) patients, respectively. One patient with neurocysticercosis and one patient with fungal meningitis died, while 8 (22.9%) had remaining neurologic sequelae. The etiology was unknown in 13 patients (37.1%). Four of these patients received empirical anti-tuberculosis therapy, while 5 were treated empirically with acyclovir.

Conclusion
Parasite infections, especially neurocysticercosis and toxocariasis, were the most common cause of eosinophilic meningitis in South Korean patients. Fungal meningitis, while relatively rare, is often aggressive and should always be considered when searching for the cause of eosinophilic meningitis.

Disclosures
All Authors: No reported disclosures
352. Seronegative Relapse of Brucellosis in the Central Nervous System
Authors: Papadopoulos Vassilis E , Tountopoulou Argyro , Patas Kostas , Vakrakou Aegli , Koropouli Eleftheria , Vassilopoulou Sophia , Mitsikostas Dimos 
Published: January 2021

Abstract

Background
Brucellosis is the most common zoonotic infection in the world. High risk areas include the Mediterranean Basin, Eastern Europe and the Middle East. Clinical presentation is quite heterogenous.
CNS involvement (neurobrucellosis) varies widely, from 0,5 to 25%. This reflects a high prevalence in endemic areas and the lack of established criteria for a diagnosis. We present a patient with a seronegative relapse of brucellosis, confined in the CNS, identified by Brucella IgG ELISA and 16S rRNA sequencing.

Methods
Case Report

Results
A 60-year-old man, farmer, with a history of systematic brucellosis two years before admission, presented with high fever, headache and agitation. A serum agglutination test and anti-Brucella IgG ELISA were negative at baseline. Spinal tap revealed lymphocytosis and low glucose. CSF culture was negative. The patient received ceftriaxone, ampicillin and acyclovir with an initial remission. A week later the patient’s symptoms relapsed. Administration of ceftriaxone and acyclovir was reinitiated with clinical improvement, however, lymphocytic meningitis persisted even after 15 days of treatment.
Brain MRI demonstrated nonspecific white matter hyperintensities and severe meningitis as identified by contrast-enhanced 3D Flair MRI. CSF oligoclonal bands showed intrathecal immunoglobin synthesis. CSF agglutination tests and CSF IgG ELISA were positive for Brucella. Though CSF PCR for Brucella was negative, 16S rRNA sequencing revealed the presence of Brucella spp. Patient was treated with ceftriaxone and dexamethasone and despite an initial worsening of neurological symptoms of tremor, loss of balance, hearing loss and diplopia, a clinical remission was achieved after a month and a laboratory remission after eight months of treatment.
Brain MRI: 3D Flair Sequence with Contrast Enhancement

Table. CSF Parameters

Conclusion
Neurobrucellosis presents with a variety of clinical symptoms and it should always be considered in neurological patients in highly endemic areas. Establishing a diagnosis is challenging. In our patient, CSF oligoclonal bands and the agglutination test in the CSF helped in achieving a diagnosis, suggesting their possible role in the diagnostic criteria. Although still under debate, the use of corticosteroids in our patient as well as the prolonged use of ceftriaxone in the therapeutic regime were crucial.

Disclosures
All Authors: No reported disclosures
366. Characteristics and Outcomes of COVID-19 Patients with Fungal Infections
Authors: Herc Erica , Yared Nicholas F , Kudirka Adam , Suleyman Geehan 
Published: January 2021

Abstract

Background
There is concern that patients with coronavirus disease 2019 (COVID-19) are at risk of developing secondary bacterial and fungal infections; however, data on the clinical characteristics and outcomes of COVID-19 patients with fungal infections are limited. We evaluated the risk factors and mortality of hospitalized COVID-19 patients with fungal infections.

Methods
This was a retrospective chart review of 51 patients with fungal infections at an 877-bed teaching hospital in Detroit, Michigan from March through May 2020. Demographic data, comorbidities, complications, treatment, and outcomes, including relapse, readmission and mortality were collected. We performed a descriptive analysis.

Results
A total of 51 patients with fungal infections were included, in which 31 (60.8%) had confirmed or suspected COVID-19 infection. Of the COVID-19 patients, the average age was 66 years and the majority (54.9%) were female. The average length of stay (LOS) was 29.3 days. Aspergillus sp. (2 A. fumigatus, 1 A. niger) were isolated in 3 (10%) patients while 23 (74.2%) had candidemia diagnosed via blood culture or T2Candida® Panel. One had a positive serum galactomannan. The average time from admission to diagnosis was 13 days. Significant comorbidities included hypertension (74%), diabetes (51.6%), coronary artery disease (25.8%), congestive heart failure (32.2%), chronic kidney disease (22.6%), and malignancy (16.1%). Most patients received steroids (83.9%) and broad-spectrum antibiotics (80.6%), had a central line (80.6%), and required intensive care unit management (90%). Only 71% were treated with antifungals. One patient with candidemia relapsed due to poor source control; two were readmitted within 30 days. In-hospital mortality rate was 51.6% among COVID-19 patients.

Conclusion
COVID-19 patients with fungal infections had multiple comorbidities, prolonged hospitalization and predisposing risk factors for fungal infections with a high in-hospital mortality rate. Prevention of fungal infections in COVID-19 patients is paramount.

Disclosures
All Authors: No reported disclosures