bluuebunny/crossref_metadata_2025_split huggingface dataset:
1243. Eravacycline in Bacteremia: A Case Series
Authors: Andrade Justin A , Kosalka Robert , Truong James , Rosenberg Joshua R 
Published: December 2021

Abstract

Background
Eravacycline (ERV) is FDA-approved for the treatment of complicated intra-abdominal infections, but there is limited experience for non-FDA approved indications.

Methods
We present five cases that utilized ERV for treatment of bacteremia.

Results
Patient 1 in septic shock (SS) started on vancomycin (VAN) and ceftazidime-avibactam (CZA). Blood culture (BC) finalized to E. coli and regimen narrowed to CZA. On day 9, gram-positive cocci in chains in BC grew and VAN was added. BC finalized to VRE faecium and regimen was modified to ERV on day 12. Repeat BC on day 15 finalized to no growth with no recurrence of bacteremia until discharged (day 78). Patient 2 treated for MSSA bacteremia with cefazolin and subsequent K. pneumoniae VAP treated with ceftriaxone (CRO) (day 18-26). On day 27, meropenem (MEM) was initiated for gram-negative bacteremia and started on IV trimethoprim/sulfamethoxazole (TMP/SMX) the following day for pneumonia caused by TMP/SMX-susceptible S. maltophila. BC finalized on day 29 to S. maltophila resistant to TMP/SMX, regimen modified to ERV. Repeat BC on day 30 finalized to no growth and ERV was continued until day 42 with no recurrence of bacteremia; however, patient died on day 45. Patient 3 with renal failure and on day 11, CRO started for SBP prophylaxis. On day 13, switched to daptomycin and cefepime (FEP) as patient was febrile and BC repeated. BC finalized to VRE faecium and was started on ERV on day 17 and completed a 7-day course with no recurrence of bacteremia; however, patient died on day 34. Patient 4 initially treated for bacterial superinfection with CRO and azithromycin, and subsequent worsening pneumonia treated with VAN and MEM (day 10-17). On day 19, patient was febrile and treated with VAN and FEP until day 27. Repeat BC on day 29 finalized to VRE species and modified to ERV on day 32. ERV continued for a 7-day course and was discharged with no repeat BC obtained to confirm clearance. Patient 5 in SS started on VAN and MEM. On day 3, BC on admission finalized to VRE faecium and therapy switched to ERV. Repeat BC taken on day 3 after ERV initiation were negative. Discharged to complete two-week course of ERV.

Conclusion
ERV may be an option for bacteremia as demonstrated by clearance in four of five cases. More studies must be conducted as these reports show variable clinical outcomes.

Disclosures
Joshua R. Rosenberg, MD, Allergan/Abbvie (Consultant)La Jolla/Tetraphase (Consultant)Melinta (Consultant)Merck (Consultant)Paratek (Consultant)Sanofi (Consultant)Shionogi (Consultant)
1244. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against MDR Enterobacterales and Pseudomonas aeruginosa Collected in Latin America During the ATLAS Global Surveillance Program 2018-2019
Authors: Lob Sibylle , Hackel Meredith , 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 that can inhibit class A, C, and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America.

Methods
Non-duplicate clinical isolates were collected in 2018-2019 in 10 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP).

Results
The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates for the studied species ranged from 16.3% among E. cloacae to 35.7% among K. pneumoniae. CAZ-AVI was active against 98% of Enterobacterales isolates and maintained activity against 74-98% of MDR isolates of the examined Enterobacterales species. Only tigecycline showed higher activity. Among P. aeruginosa, CAZ-AVI was active against 87% of all isolates and 47% of MDR isolates; no other studied drug was more active. The three most common MDR phenotypes among Enterobacterales were 1) R to ATM, FEP, and LVX (n=544, 44.8% of all MDR Enterobacterales; 100% susceptible (S) to CAZ-AVI), 2) R to ATM, FEP, LVX, and TZP (n=150, 12.4% of all MDR Enterobacterales; 99.3% S to CAZ-AVI), and 3) R to all sentinel drugs except AMK and CST (n=145, 11.9% of all MDR isolates; 78.6% S to CAZ-AVI). The three most common MDR phenotypes among P. aeruginosa were 1) R to all sentinel drugs except CST (n=85, 19.7% of all MDR isolates; 24.7% S to CAZ-AVI), 2) R to all sentinel drugs except AMK and CST (n=42, 9.7% of all MDR isolates; 66.7% S to CAZ-AVI), and 3) R to AMK, LVX, and MEM (n=37, 8.6% of all MDR isolates; 24.3% S to CAZ-AVI).

Conclusion
These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacterales and P. aeruginosa collected in Latin America.

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)
1249. Metabolomic Profile of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus (hVISA) in Latin-American MRSA Isolates
Authors: Castro-Cardozo Betsy E , Cala Monica , Espitia-Acero Catalina , Rios Rafael , Leon Lizeth , Arias Cesar A , Rincon Sandra , Reyes Jinnethe , Diaz Lorena , Diaz Lorena 
Published: December 2021

Abstract

Background
Vancomycin (VAN) is a first-line therapeutic option in severe infections caused by MRSA in Latin-America (LA). Development of reduced susceptibility to VAN has been associated with multiple changes in genes encoding pathways for cell wall metabolism and envelope stress responses. Nevertheless, a detailed and coherent mechanistic model to explain the phenotype remains elusive. To gain further insights into the hVISA phenotype, we sought to explore the metabolomic profile of hVISA isolates from LA.

Methods
The undirected profile of intracellular S. aureus metabolites was analysed in four clinical isolates (two hVISA and two VSSA [Vancomycin susceptible S. aureus]) belonging to the Chilean/Cordobes clone-ST5 (the predominant hVISA lineage in LA), and two reference strains Mu3 and N315. The metabolites were obtained in mid-exponential growth phase in trypticase soy broth in five independent replicates. The metabolites were determined by reverse phase liquid chromatography and hydrophilic interaction. The metabolic profile was determined by variable importance in the projection score (VIP &gt; 1). The differences between hVISA and VSSA were maximized by orthogonal partial least squares discriminant analysis (OPLS-DA) and the affected metabolic pathways were identified with MetaboAnalyst.

Results
Among the differences identified in the metabolic profiles of hVISA respect to VSSA, 69 metabolites were relevant. Of these, 47 were fatty acids (including glycerol), 7 amino acids and 6 nucleosides (Table 1). These changes mainly impact the biosynthesis of amino acids derived from pyruvate since tyrosine, valine and leucine, had a reduction of 34%, 57% and 41% in hVISA compared to VSSA, respectively, which suggests alterations of the acid cycle tricarboxylic (TCA). Additionally, a reduction in purine and pyrimidine metabolism in hVISA was identified with reduction of nucleosides and dinucleotides derived from the pentose phosphate pathway.
Table 1. Metabolites with higher VIP scores in the comparison of the hVISA and VSSA profile

Conclusion
We were able to observe metabolic alterations in TCA, pentose phosphate pathway and purine intermediates in hVISA-ST5 isolates. Our results support that gluconeogenesis and biosynthesis of carbohydrates and nucleic acids are the main pathways involved in the reduced susceptibility to VAN as reported in VISA isolates.

Disclosures
Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support) Lorena Diaz, PhD , Nothing to disclose
1250. Development of Linezolid and Daptomycin Resistance in Vancomycin Resistant Enterococcus faecium (VRE) during prolonged treatment for Intraabdominal Abscess
Authors: Al-Heeti Omar , Joshi Tejas , Moore William Justin , Gatesy Samuel W , Pincus Nathan B , R Bachta Kelly E 
Published: December 2021

Abstract

Background
Vancomycin-resistant enterococci (VRE) are nosocomial pathogens with extensive intrinsic and acquired antimicrobial resistance (AMR) mechanisms. We report a case in which intraabdominal (IA) and blood cultures grew linezolid and daptomycin resistant VRE (DLVRE).

Methods
We report a case of DLVRE bacteremia after prolonged treatment with linezolid and daptomycin.

Results
The patient was a 65-year-old female with a history of multiple abdominal surgeries who presented for elective incisional hernia repair. Her post-operative course was complicated by the development of loculated IA abscesses. A drain was placed into the largest abscess, and aspiration cultures were polymicrobial containing vancomycin-resistant E. faecium (Isolate 1). The patient was treated meropenem, fluconazole and linezolid for 6 weeks. Clinical and radiographic improvement was achieved. However, 4 days after competing antibiotics she developed recurrent abdominal pain and a leukocytosis. Daptomycin was chosen out of concern for long-term linezolid toxicity and IA cultures demonstrated new linezolid resistance (Isolate 2, LVRE). After an additional three weeks of therapy, she developed a catheter-associated bloodstream infection (CLABSI). Blood cultures revealed daptomycin-resistant LVRE bacteremia (Isolate 3, DLVRE). She was started empirically on a combination of ceftaroline and daptomycin, her PICC line removed, and her blood cultures cleared. Her antibiotic course is presented in Figure 1 and resistance patterns of the VRE in Table 1.

Conclusion
In this patient, an IA abscess known to harbor VRE developed resistance to both linezolid and daptomycin during prolonged treatment with both agents. Ultimately, the patient experienced an episode of CLABSI DLVRE. Limited data exists on appropriate antibiotic choice in such challenging situations. Based on prior clinical and experimental data, we elected to use daptomycin in conjunction with ceftaroline for synergy, and the patient achieved the desired clinical response, clearance of her blood cultures and diminishing size of her IA abscess. Further work is needed to elucidate the best course of treatment for patients with VRE requiring long-term antibiotic therapy and for those who have developed extensively drug-resistant E. faecium.

Disclosures
All Authors: No reported disclosures
1255. External Validation and Systematic Quantification of the Predictive Performance of Carbapenem Resistant Enterobacterales Risk Prediction Models in Hospitalized Patients
Authors: Farkas Andras , Yassin Arsheena , Sy Hendrik , Huang Kristy , Stein Iana , Acquah Samuel , Radparvar Sara , Stavropoulos Christine , Mathew Joseph 
Published: December 2021

Abstract

Background
Accurately predicting the presence of a carbapenem resistant enterobacterales (CRE) in hospitalized patients presents itself as an opportunity that would support timely initiation of CRE active agents. The aim of this study is to determine how reliably the existing risk prediction models identify patients likely to require empiric anti-CRE treatment, preliminary results of which are presented herein.

Methods
A systematic search identified all existing CRE prediction models for validation in our patient population. Medical records of hospitalized patients within the Mount Sinai Health System in New York were subsequently reviewed. Data was gathered on model predictors, baseline demographics, clinical information, microbiology results, antibiotic utilization history and index infection. Besides calculating the AUROC, the main outcome of our study was to establish optimal prediction score cutoffs and false positive rates (FPR) where corresponding model performance maintains a false negative rate (FNR) of &lt; 10%, &lt; 20% and &lt; 30%, respectively.

Results
12 models were retained for validation. We identified 106 patients, 41 of which were treated for a CRE infection. Previous admission, organ transplantation, CKD, infection type, and carbapenem use were baseline variables that significantly differed between the groups treated for a CRE or non-CRE related infection (Table 1). The models ability to discriminate varied as evidenced by the AUROC range of 0.5 to 0.77 (Figure 1), suggesting the Seligmen et al. model as the overall best. When evaluated at the pre-specified FNR intervals of &lt; 10%, &lt; 20% and &lt; 30%, the model by Lodise et al., Seligman et al., and Vazquez-Guillamet et al. produced the best FPR, respectively (Table 2).
Table 1. Baseline characchteristics

Table 2. Model Performance

Figure 1. AUROCs

Conclusion
Discriminative ability of the risk prediction models showed varying performance. The model by Lodise et al. appears to be most useful when a low risk level is deemed acceptable for failure rate, while at a moderate to high risk of missing a CRE case (20% and 30% FNR), the methods by Seligman and Vazquez-Guillamet et al. are most desirable as they minimize the chance of over-treatment. Additional work to increase sample size and to evaluate the models inter-rater reliability is currently on going.

Disclosures
All Authors: No reported disclosures
1256. Clinical Response by Minimum Inhibitory Concentrations in Carbapenem-Resistant Pseudomonas aeruginosa Infections under Cefiderocol Compassionate Use Program
Authors: Satlin Michael J , Fam David , Echols Roger , Longshaw Christopher , Takemura Miki , Yamano Yoshinori 
Published: December 2021

Abstract

Background
Cefiderocol (CFDC) has been developed for the treatment of serious infections caused by drug-resistant aerobic Gram-negative pathogens, including carbapenem-resistant (CR) Pseudomonas aeruginosa (CRPA). The current CFDC susceptibility breakpoints for P. aeruginosa differ between US Food and Drug Administration (FDA) and Clinical and Laboratory Standards Institute (CLSI) (Table). Data characterizing the impact of CFDC minimum inhibitory concentrations (MICs) on the clinical responses of patients treated with CFDC for CRPA are sparse.

Methods
We reviewed patients treated with compassionate-use CFDC (2 g, q8h or renally adjusted dosages) for infections caused by CRPA with no alternative treatment options. CFDC minimum inhibitory concentrations (MICs) were evaluated according to CLSI guidelines in iron-depleted cation-adjusted Müller–Hinton broth for available CRPA isolates. We then assessed physician-reported clinical responses to CFDC therapy and stratified results by CFDC MIC.

Results
There were 71 patients overall with CRPA treated with CFDC. Treatment duration ranged from 1 to 132 days. For the subset of 33 patients for whom CFDC MIC values were available, the most common infection sites were the respiratory tract (n=15), blood (n=12), and urinary tract (n=4). Patients could have had an infection at ≥1 sites and in other locations. CFDC MIC range was ≤0.03– &gt;64 µg/mL. The modal MIC value was 2 µg/mL (n=13; Table). CRPA isolates were susceptible to CFDC in 13/33 patients (39.4%) based on the FDA breakpoint (MIC ≤1 µg/mL) and in 31/33 patients (93.9%) based on the CLSI breakpoint (MIC ≤4 µg/mL). Clinical response was reported for 15/18 patients (83.3%) who had infections with CFDC MICs of 2–4 µg/mL, organisms that are considered susceptible by CLSI but not by FDA breakpoints (Table). Clinical response was reported in 6/13 patients (46.1%) with infections with CFDC MIC ≤1 µg/mL and in 1 of 2 patients (50.0%) with CFDC MIC ≥8 µg/mL (Table). 21 (63.6%) patients survived to Day 28 and there were no trends in mortality by CFDC MIC.

Conclusion
Clinical response rate was high for CRPA infections with CFDC MICs of 2–4 µg/mL, supporting the higher CLSI susceptibility breakpoint.

Disclosures
Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Research Grant or Support)BioFire Diagnostics (Research Grant or Support)Merck (Research Grant or Support)Shionogi (Consultant) David Fam, PharmD, Shionogi (Employee) Roger Echols, MD, Shionogi (Consultant) Christopher Longshaw, PhD, Shionogi (Employee) Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Yoshinori Yamano, PhD, Shionogi (Employee)
1260. In Vitro Activity of Eravacycline Against Clinically Significant Bacteria Isolated from Patients with Cancer
Authors: Gerges Bahgat , Prince Randal , Rosenblatt Joel , Reitzel Ruth A , Shelbume Samuel , Aitken Samuel L , Aitken Samuel L , Raad Issam I , Rolston Kenneth 
Published: December 2021

Abstract

Background
Bacterial infections are common in patients with cancer (PWC). Many bacteria have developed resistance to currently used antibiotics, posing therapeutic challenges. we evaluated the in vitro activity of eravacycline (a novel fluorocycline) against clinical bacteria recently (2018-2019) isolated from PWC.

Methods
All 565 isolates tested were from blood cultures. CLSI approved broth microdilution method was used. Appropriate ATCC controls were included. MIC50, MIC90, MIC ranges and percent susceptibility calculations were made using FDA breakpoints when available. Eravacycline susceptibility breakpoint for most Gram-positive organisms (GPO) is ≤ 0.06 mg/L and for Enterobacterales is ≤ 0.5 mg/L.

Results
Eravacycline had potent activity against Staphylococcus aureus (methicillin-susceptible and resistant strains), oxacillin-susceptible coagulase-negative staphylococci (CoNS) including Staphylococcus lugdunensis, viridans group streptococci, beta-hemolytic streptococci. Streptococcus pneumoniae. Bacillus spp., Corynebacterium spp., and Micrococcus spp. It was slightly less active against oxacillin-resistant CoNS, and vancomycin-susceptible Enterococcus faecalis (MIC90 0,125 mg/L respectively) and was moderately active against vancomycin-resistant Enterococcus faecium (MIC50, 0.06, and MIC90. 0.25 mg/L). Eravacycline had potent activity against Escherichia coli (including ESBL producing strains), Citrobacter spp., and non-ESBL Klebsiella spp. Eravacycline inhibited 83% of ESBL positive K. pneumoniae, 83% of Enterobacter cloacae, and 80% of carbapenem-resistant Enterobacteriaceae (CRE) isolates at ≤ 0.5 mg/L. The presence of ESBLs increased MIC90 value no more than 2 fold. Eravacycline was also active against many non-fermentative GNB (Achromobacter spp., Acinetobacter spp., Sphingomonas paucimobilis, and Stenotrophomonas maltophilia).
Table 1. Percent Susceptibility of Gram-negative isolates to Eravacycline

Table 2. Percent Susceptibility of Gram-positive isolates to Eravacycline

Conclusion
Our data demonstrate that eravacycline has promising activity against clinically significant bacterial pathogens isolated from PWC including many drug resistant strains such as CRE and non--fermentative GNB. it might play an important role in the treatment of bacterial infections in PWC and warrants clinical evolution in this setting.

Disclosures
Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support Kenneth Rolston, MD, Tetraphase Pharmaceuticals (Grant/Research Support)
1262. Salvage Therapies for Carbapenem Resistant Acinetobacter baumanii Outbreak in a Tertiary Care Center
Authors: Lai Lauren , Rose Lucia , king Madeline , Fraimow Henry , Byrne Dana D 
Published: December 2021

Abstract

Background
The 2019 Antimicrobial Resistance Threat Report cites carbapenem-resistant Acinetobacter baumanii (CRAB) as an urgent threat causing &gt; 700 deaths per year.1 Acinetobacter is unique in its ability to acquire resistance determinants and pan-resistant strains have been previously reported.2 It has the propensity to cause outbreaks, especially in critically ill populations due to its ability to survive on surfaces.3,4 In 2018, our hospital experienced a large CRAB outbreak. All strains were multi-drug resistant and most were identified by the Centers for Disease Control as containing OXA-23 ß-lactamase. Standard of care (SOC) was limited to agents with high toxicity potential, and thus we explored emerging therapies. In collaboration with Shionogi Inc., we obtained compassionate use cefiderocol as salvage therapy in patients failing SOC. We present our experience utilizing various treatments for CRAB infections during a hospital outbreak.

Methods
We performed a retrospective chart review in adult patients with a CRAB infection treated with either cefiderocol or SOC for greater than 2 days from 08/2017 - 01/2020. SOC included use &gt; 1 of the following: tigecycline, meropenem, polymyxins, amikacin, or eravacycline. At the time of our outbreak, we developed an institutional algorithm delineating which therapy to initiate depending on infection type. Demographic characteristics, illness severity scores, type of infection, and patient outcomes were evaluated.

Results
The median age [IQR] for the cefiderocol group was 57.5 [42 to 69] versus 60 [50 to 65] in the SOC group. Illness severity scores were lower in the cefiderocol group: SOFA median value [IQR] 3.5 [1.5 - 5] versus 5 [2 - 7] and CCI median value [IQR] was 3 [2.00 -3.00] versus 3 [2 -5] (Table 1). In hospital mortality was similar in both groups with the cefiderocol group having 50% in hospital mortality versus 42.2% in the SOC group. 28-day mortality was 62.6% in the cefiderocol group versus 42.4% in the SOC group (Table 2).

Conclusion
Cefiderocol may be a viable option for salvage therapy for CRAB infection. Our cohort illustrated similar outcomes as standard therapy. This study is limited by a small sample size receiving cefiderocol and the significant delay associated with obtaining cefiderocol at the time.

Disclosures
Lucia Rose, PharmD, Allergan (Speaker’s Bureau)Paratek (Employee) Madeline king, PharmD, Tetraphase (Speaker’s Bureau) Henry Fraimow, MD, Astellas pharma (Grant/Research Support)Merck (Grant/Research Support)Shionogi (Consultant, Grant/Research Support, Scientific Research Study Investigator) Dana D. Byrne, MD, MSc, Merck (Employee)