bluuebunny/crossref_metadata_2025_split huggingface dataset:
1263. In Vitro Activity of Ceftazidime-avibactam and Comparator Agents against Enterobacterales and Pseudomonas aeruginosa Collected from Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2017-2019
Authors: Lob Sibylle , Hackel Meredith , Stone Gregory , Sahm Daniel F 
Published: December 2021

Abstract

Background
Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2017-2019.

Methods
A total of 48193 Eba and 15376 Pae non-duplicate clinically significant isolates, including 9224 Eba and 1808 Pae isolated from bloodstream infections, were collected in 53 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/ml AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes.

Results
Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.4-3.4% lower among Eba and Pae from bloodstream infections compared to isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and the CAZ-NS subset (MIC90, 0.5-4 µg/ml, 91.7-97.4% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) as 98.1% of MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. None of the tested comparators exceeded the activity of CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/ml, 89.7% S). Activity was reduced against CAZ-NS and MEM-NS subsets (55.9-63.0% S), which included isolates carrying MBLs, but exceeded the activity of CAZ against MEM-NS and MEM against CAZ-NS by 26-28 percentage points. Amikacin was the only tested comparator that demonstrated comparable activity against Pae bloodstream isolates.
Results Table

Conclusion
CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1264. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected &lt; 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2016-2019
Authors: Kazmierczak Krystyna , Lob Sibylle , Stone Gregory , Sahm Daniel F 
Published: December 2021

Abstract

Background
Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against presumed community-acquired (CA; cultured &lt; 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program.

Methods
6654 non-duplicate isolates were collected in 52 countries in Europe (n=3423), Latin America (n=1323), Middle East/Africa (n=1177), and Asia/Pacific (excluding China; n=731) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1687), urinary tract (UTI; n=1631), bloodstream (BSI; n=1149), skin and soft tissue (SSTI; n=1122), and intra-abdominal (IAI; n=981) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2021 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes.

Results
The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (97.8% susceptible (S)) and Psa (92.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 95.4-99.2% among CA Ent from different infection types and were reduced 0.6-1.3% among HA isolates from LRTI, UTI, SSTI, and IAI. Susceptibility to CAZ-AVI was also similar (92.6-95.8% S) among CA Psa from different infection types and was reduced 1.2-7.0% among HA isolates. Larger differences in susceptibility were typically seen for the tested comparator β-lactams. For Ent, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, while the pattern was less clear for Psa.
Results Table

Conclusion
CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients.

Disclosures
Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1265. In Vitro Activity of Aztreonam-Avibactam against Klebsiella pneumoniae Isolates Analyzed by Epidemic Lineage and Hypervirulence Factors Collected in China as Part of the ATLAS Global Surveillance Study in 2019
Authors: Estabrook Mark , Kazmierczak Krystyna , Arhin Francis , Sahm Daniel F 
Published: December 2021

Abstract

Background
Hypervirulent Klebsiella pneumoniae (hvKp), unlike classical K. pneumoniae (cKp), are often responsible for community-acquired infections in otherwise healthy individuals. The acquisition of hypervirulence genes by sequence type 11 (ST11) carbapenem-resistant (CR) Kp endemic in Asia is a grave threat. Aztreonam-avibactam (ATM-AVI) is a monobactam combined with a β-lactamase inhibitor for the treatment of infections caused by Enterobacterales isolates that carry Class A, B, C and some Class D β-lactamases.

Methods
487 K. pneumoniae isolates were collected from 17 sites in China in 2019 as a part of the ATLAS global surveillance study. 220 isolates with MICs &gt;1 µg/ml to meropenem (MEM), ceftazidime or ATM were selected for whole genome sequencing (Illumina Hiseq 2x150 bp reads). Analyses were carried out using the CLC Genomics Workbench (Qiagen). Presence of the aerobactin synthesis locus differentiated hvKp and cKp. Antimicrobial susceptibility was determined by CLSI broth microdilution.

Results
Of the 487 isolates, MIC90 values for ATM-AVI (0.5 µg/ml; Table) were lower than those for any comparator tested, with only two isolates testing with MIC &gt;4 µg/ml. Of the isolates sequenced, 82/220 (37.3%) were ST11. 53/82 (64.6%) of these ST11 isolates were hvKp (ATM-AVI, MIC90 1 µg/ml; range, 0.25-4 µg/ml) and showed percentages of susceptibility &lt; 90% to three last-line agents (0% MEM-susceptible (S); 18.9% amikacin (AMK)-S; 88.7% tigecycline (TGC)-S). Isolates of other STs (Non-ST11) were less frequently identified as hvKp (24/138, 17.4%) and more Non-ST-11 hvKp and cKp alike were S to MEM and AMK relative to isolates of ST11 (75.0-86.8% MEM-S; 83.3-96.5% AMK-S). Likewise, the ATM-AVI MIC90 value (0.25 µg/ml) was 4-fold lower for Non-ST11 isolates.
Results Table

Conclusion
CR ST11 hvKp represented at least 10.9% of the collected Kp isolates. ATM-AVI retained potent in vitro activity against these isolates which displayed resistance to a range of last-line agents. CST and TGC also displayed some activity but are limited in utility due to nephrotoxicity and poor accumulation in blood, respectively. The spread of virulence factors leading to the complicated clinical presentation of hvKp infection into multidrug-resistant lineages warrants continued surveillance.

Disclosures
Mark Estabrook, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1266. Melatonin for Renal Protection of Patients Treated with Polymyxin B: A Double Blind Randomized Clinical Trial
Authors: Rigatto Maria Helena , Bergo Pedro , Baldissera Giulia , Beck Eduarda , David Leonardo , Santoro Lucas , Falci Diego Rodrigues , Caumo Wolnei , Zavascki Alexandre 
Published: December 2021

Abstract

Background
Polymyxins are one of the last resort treatments for carbapenem resistant gram-negative infections. Nephrotoxicity is its main adverse effect and has been related to oxidative stress mechanisms. Melatonin was associated to reduction in polymyxins nephrotoxicity in animal studies. Our objective is to evaluate the effect of melatonin on renal protection of patients receiving polymyxin B.

Methods
We did a single center, double blind, randomized clinical trial (NCT03725267) of melatonin 30mg versus placebo for patients treated with polymyxin B from October 2018 to April 2021, in Porto Alegre, Brazil. Patients ≥18 years old, receiving polymyxin B for ≤48 hours, who accepted informed consent terms were included and excluded if intensive care unit (ICU) admission at enrollment, estimated glomerular rate estimated glomerular rate &lt; 10ml/min, dialysis or previous melatonin use. Treatment with melatonin or placebo was randomized in blocks of 4 and maintained until the end of polymyxin B treatment of for a maximum of 14 days. Our main outcome was any level of nephrotoxicity by RIFLE score. Secondary outcomes were renal failure and need for dialysis. We estimated a sample size of 100 patients, however the study had to be stopped earlier due to recruitment restrictions imposed by the COVID-19 pandemic.

Results
Eighty-eight patients were randomized, 44 received melatonin and 44 received identical placebo pills. Patients had a mean age of 63.6±17.3 years, 60.2% were male, and had a median Charlson index of 5 (3-8.3). Most infections (79.5%) were microbiologically confirmed, having 68.6% Klebsiella sp isolated. Urinary tract accounted for47.7% of infection sites. Median time of polymyxin B therapy was 9.1±6.6 days. Combination therapy was prescribed for 89.8% of patients and 38.6% received at least another nephrotoxic drug. All variables were equally distributed among groups. Nephrotoxicity rates occurred in 23 of 44 (52.3%) in both groups, P=0.99. Patients who developed renal failure were 8(18.2%) vs 9(20.5%) and dialysis occurred in 4(9.1%) vs 5 (11.4%) of melatonin and placebo groups respectively.

Conclusion
Melatonin did not show a clinically significant renal protective effect in patients treated with polymyxin B.

Disclosures
Maria Helena Rigatto, MD, PhD, CNPq (Grant/Research Support) Diego Rodrigues Falci, MD, MSc, PhD, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)GSK (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)MSD (Speaker’s Bureau)Pfizer (Speaker’s Bureau)United Medical (Speaker’s Bureau, Other Financial or Material Support) Alexandre Zavascki, MD, PhD, Pfizer (Grant/Research Support)
146. Intact Sense of Taste and Smell During COVID-19 Infection Is Associated with Absence of of SARS-CoV-2 Spike Protein Antibody Responses within 3 Months of Symptomatic Illness
Authors: Wilson James M , Gillani Sheena , Bencshop Robert , Poorbaugh Josh , Nirula Ajay , Zhang Lin , Keckler Kody , Weber Kathleen , Morack Ralph , Beasley Stephanie , Brothers Jennifer , Huhn Gregory 
Published: December 2021

Abstract

Background
Although studies show most COVID-19 survivors have post-infection immunity against SARS-CoV-2 that could prevent re-infection, there is still a need to identify the breadth of antibody (Ab) responses associated with clinical phenotypes. We characterized Ab profiles at the estimated peak of Ab diversity among adults with recovered SARS-CoV-2 infections and determined their relationships with clinical factors.

Methods
From April-June 2020, 41 health system employees with PCR-confirmed symptomatic COVID-19 infection enrolled 8-10 weeks after symptom onset. Symptom questionnaires including baseline demographics, COVID-19 symptoms, disease severity, and disease duration were collected and plasma samples were assayed using a custom Luminex Multiplex platform (Figure 1) to measure the antibody response against 20 COVID-19 related antigens (Figure 2). Differences in Ab profile titers among different groups were tested using nonparametric t test and Benjamini-Hochberg adjustment for multiplicity. Associations were considered significant at FDR&lt; 0.05.

Figure 1: Description of the Luminex Serology Assay

Figure 2: List of the COVID-19 Related Antigens and Controls Measured

Results
Mean age was 48 years (range 27-68), with 51% female, 37% White, 32% Black, 29% Asian, and 17% LatinX. Ab profiles (Figure 3) showed 100% cross-reactivity with related alpha and beta coronavirus, and 95% with SARS-CoV-1. 78% had Abs against SARS-CoV-2 nucleocapsid protein (NCP). However, 29% of patients had no immune response against the four spike protein epitopes. These participants also reported fewer symptoms, including no cases of anosmia/ageusia, suggesting mild illness. Anosmia/ageusia, fever, and cough associated significantly with higher Ab titers (Figure 4).

Conclusion
Broad immune responses to various SARS-CoV-2 and related antigens were found among a heterogeneous patient population. However, less than 3 months after symptom onset, protective Ab responses to SARS-CoV-2 spike proteins were not detected in nearly one-third of recovered patients, primarily with mild infection. Intact sense of smell and taste demonstrated the greatest association with loss of seroprotective SARS-CoV-2 Ab responses, which may be clinically useful to predict post-infection immunity. Next steps include comparing the magnitude of Ab responses following full series completion with mRNA vaccination among this cohort.

Disclosures
Robert Bencshop, PhD, Eli Lilly (Employee) Josh Poorbaugh, PhD, Eli Lilly (Employee) Ajay Nirula, MD/PhD, Eli Lilly (Employee, Shareholder) Lin Zhang, PhD, Eli Lilly and Company (Employee, Shareholder) Stephanie Beasley, BA, Eli Lilly (Employee)
1268. In Vitro Activity of Ceftazidime-Avibactam and Comparators against KPC-Producing Enterobacterales and Pseudomonas aeruginosa Collected in China as Part of the ATLAS Global Surveillance Program in 2019
Authors: Wise Mark G G , Kazmierczak Krystyna , Stone Gregory , Sahm Daniel F 
Published: December 2021

Abstract

Background
Among Gram-negative bacteria, the rapid spread of carbapenemases has limited therapeutic options. Klebsiella pneumoniae carbapenemase (KPC), an Ambler class A serine β-lactamase, presents a particular challenge as it has become widespread, first identified in an isolate collected in the United States and thereafter moving throughout the world, including China. Fortunately, the β-lactamase inhibitor avibactam is a potent inhibitor of KPC, rendering many Enterobacterales and some P. aeruginosa isolates that carry KPC susceptible to ceftazidime-avibactam (CAZ-AVI) in vitro. This study reports on the in vitro activity of CAZ-AVI and comparators against Enterobacterales and P. aeruginosa isolates collected in China as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program in 2019.

Methods
1,443 non-duplicate Enterobacterales and 522 P. aeruginosa isolates were collected from 17 clinical sites in China in 2019. Susceptibility testing was done using broth microdilution according to CLSI guidelines and interpreted using CLSI 2021 breakpoints. 143/177 meropenem non-susceptible Enterobacterales isolates and 150/187 meropenem non-susceptible P. aeruginosa isolates were interrogated by whole genome sequencing (WGS; Illumina 2x150 bp reads).

Results
Enterobacterales isolates exhibited higher % susceptibility (% S) to CAZ-AVI than all comparators tested (96.0% S; Table). The addition of AVI to CAZ resulted in an increase in susceptibility from 61.3% to 96.0% in the overall collection of Enterobacterales isolates. 96.0% of KPC-positive Enterobacterales, and 67.8% of the meropenem non-susceptible sub-population were susceptible to CAZ-AVI, against which comparators were less active (≤42.9 % S). Among P. aeruginosa isolates, 89.8% were susceptible to CAZ-AVI, more than for any comparator except amikacin (AMK; 94.4% S). Against meropenem non-susceptible and KPC-carrying P. aeruginosa sub-populations more were susceptible to CAZ-AVI (75.9% and 83.3% S, respectively) and AMK (87.2% and 100% S, respectively) than to other comparators (≤40.6% and ≤8.3% S, respectively).
Results Table

Conclusion
CAZ-AVI demonstrated very good in vitro activity against Enterobacterales and P. aeruginosa isolates from China, including those that harbor KPC.

Disclosures
Mark G G. Wise, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1269. Infection, Clinical Syndromes and Antimicrobial Resistance by Aeromonas species: 13-Year Experience with an Emerging Pathogen at a Tertiary Care Center
Authors: Pineda-Reyes Roberto , Orndorff Joseph , Reynoso David 
Published: December 2021

Abstract

Background
Aeromonas spp. are emerging pathogens that cause a wide breadth of clinical syndromes, ranging from acute gastroenteritis to skin and soft tissue infections, sepsis, and “flesh-eating” necrotizing fasciitis. Aeromonads have been associated with natural disasters and have predominance in estuarine ecosystems, generating a negative impact on the fishing industry and aquaculture, as well as morbidity and mortality in human populations at risk. Antimicrobial resistance patterns differ by geographic locations worldwide, and studies to guide the therapy in the era of multidrug resistance are lacking in the US.

Methods
A retrospective case series was designed to chart review all adult subjects who had culture proven Aeromonas spp. infections during the period 2008-2020. Demographic data, water exposure, clinical syndromes on presentation, origin (community-acquired vs. nosocomial) and severity of infection, antibiograms, empirical antibiotics, time-to-appropriate therapy, and treatment outcomes were collected.

Results
Eighty-two subjects were included in the analysis. Demographic and clinical data is summarized in Table 1. Near 20% individuals had water exposure, including 53% of those with traumatic wound infections. Skin and soft tissue infection (including traumatic and surgical wound infections) was the most frequent clinical syndrome (51.2%). Sepsis was present on admission in 33% inpatients. Appropriate antibiotics were instituted in a median of 2 days (IQR=1-5), and the most prescribed empiric agents were piperacillin-tazobactam (48%) and meropenem (13.3%). Most isolates were susceptible to cefepime (70/71, 98.6%), levofloxacin (72/78, 92.3%) and TMP-SMX (69/78, 88.5%). Resistance to meropenem was reported in 18/31 isolates (58.1%) after 2015. Treatment failure was identified in 32.3% cases.

Most cases (55%) were encountered during the months of spring and summer, which have warmer temperatures and seasonal heavy rains. Tropical storms caused significant flooding in the Galveston Bay area and Southeast Texas during the summer of 2015, which interestingly coincides with the high number of cases. However, following Hurricane Ike in 2008 or Hurricane Harvey in 2017, the number of cases did not significantly increase.

Conclusion
Aeromonads are emerging pathogens that cause mainly intraabdominal and skin and soft tissue infections. Their incidence is seasonal (55% cases in spring and summer) and it is associated with water exposure in more than half of those with traumatic wound infections. In subjects with specific risk factors, the use of carbapenem-sparing strategies, such as 3rd or 4th generation cephalosporins, fluoroquinolones or TMP-SMX, may improve outcomes.

Disclosures
All Authors: No reported disclosures
1270. Molecular Characterization of Carbapenemase Producing Enterobacterales, Acinetobacter spp. and Pseudomonas spp. in Nosocomial and Community-acquired Clinical Isolates in Bogota, Colombia
Authors: Reyes Luis F , Bustos-Moya Ingrid G , Josa Diego , Gamboa-Silva Enrique , Ibañez-Prada Elsa Daniela , Africano Hector , Urrego-Reyes Juan , Beltrán Claudia , Leon Sebastian , Ruiz-Cuartas Alejandra , Baron Oscar , Leal Rafael , Hawkey Jane , Wyres Kelly , Stewardson Andrew 
Published: December 2021

Abstract

Background
Antimicrobial resistance (AMR) in low-income and middle-income countries (LMICs) is a public health problem. AMR is a concerning problem in Gram-negative bacteria such are Enterobacterales, which are frequently carbapenem-resistant pathogens (CRP), and few therapeutic options are available. However, scarce data is known regarding the clinical, molecular characteristics, and clinical outcomes of patients infected with carbapenem-resistant pathogens in LMICs. Thus, this study will attempt to bring novel data in these regards.

Methods
This is a retrospective cohort study conducted in two reference hospitals in Colombia, South America. All consecutive patients infected with CRPs between 2017 and 2021 were included. Clinical data were gathered by retrospective chart review. Bacterial pathogens and antibiotic susceptibility were prospectively identified and stored by each hospital. Molecular characterization was performed by PCR in isolated bacteria.

Results
A total of 220 patients were included. The mean (SD) age was 60.6 (18.4) years, and 32% (71/220) were female. The most frequently identified CRPs were Pseudomonas aeruginosa (85/220, 39%) and Klebsiella pneumoniae (81/220, 37%). CRPs were most frequently identified in urine, blood, and respiratory samples (Figure 1). Community-acquired infections were frequently diagnosed in patients infected with CRPs in our study (73% [161/220]), and most of the patients were admitted to the ICU (163/220, 74%). The in-hospital mortality rate was 28% (62/220) and 38% (62/163) in ICU admitted patients. PCR was carried out in 105 CRP; KPC (69%, 73/105) and VIM (37%, 39/105) were the most frequently identified mechanisms. Of the K. pneumoniae isolates with PCR assessment, 94% (33/35) had KPC and 3% (1/35) had VIM. In contrast, in P. aeruginosa isolates with PCR assessment, 53% (29/54) had KPC and 59% (32/54) had VIM. Seven (13%) patients infected with P. aeruginosa had both KPC and VIM genes identified.

Conclusion
The most frequently identified carbapenem-resistant pathogens in these two Colombian reference hospitals were P. aeruginosa and K. pneumoniae, with high mortality rates. KPC was the most commonly identified mechanism of carbapenem resistance in our cohort.

Disclosures
All Authors: No reported disclosures