bluuebunny/crossref_metadata_2025_split huggingface dataset:
2247. Real-world Experience with Meropenem–Vaborbactam (M/V) for Treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections
Authors: Shields Ryan K , McCreary Erin K , Marini Rachel V , Kline Ellen G , Jones Chelsea E , Hao Binghua , Clancy Cornelius J , Nguyen Minh-Hong 
Published: October 2019

Abstract

Background
M/V demonstrates in vitro activity against KPC-producing CRE, but real-world clinical experience is limited.

Methods
Patients treated for > 48 hours with M/V for CRE infections were included. Success was defined as improved symptoms, absence of recurrent infection, and survival at 30 days. Microbiologic failures (MF) were defined as isolation of the same species post-treatment (tx). KPC and ompK36 mutations were detected by sequencing of PCR products.

Results
19 patients were included; 58% were men; median age was 53. 11% were transplant recipients and median Charlson score was 3 (range: 0–10). Infection types included bacteremia (n = 7), pneumonia (6; 5 ventilator-associated), soft tissue (2), tracheobronchitis (2), intra-abdominal (1), and pyelonephritis (1). 68% of patients were in the ICU; median APACHE II and SOFA scores were 18 (7–40) and 4 (1–13), respectively. CR pathogens included K. pneumoniae (14), K. oxytoca (2), E. coli (2), and C. freundii (1); 89% harbored KPC, including KPC-2 (6), KPC-3 (10), and KPC-3 with a D179Y mutation (1). All were susceptible to M/V (median MIC = 0.03 µg/mL [0.015–0.12]). Median duration of tx was 8 days (3 – 28); 89% received monotherapy. Success and survival rates at 30d were 63% and 89%, respectively. Failures were due to death (2), recurrent infection (2), worse symptoms (2), and persistent bacteremia (1). Success rates for bacteremia and pneumonia were 57% and 67%, respectively. MF within 90 days occurred in 32% due to K. pneumoniae (5) or E. coli (1). MF were classified as intra-abdominal abscess (3), pneumonia (1), and respiratory (1) or urinary (1) colonization. The median time to MF was 32 days (15 – 67). M/V MICs were increased ≥8-fold against 67% (4/6) of recurrent isolates. 1 pt developed intra-abdominal infection due to M/V non-susceptible KPC-3 K. pneumoniae isolate (MIC = 8) following a 12-day of M/V; the recurrent isolate differed from the parent by an IS5 insertion in the ompK36 gene promoter. M/V was well-tolerated, 1 patient developed eosinophilia.

Conclusion
In this cohort of critically-ill patients with CRE infection, tx with M/V yielded outcomes comparable to prior cohorts treated with ceftazidime–avibactam. M/V non-susceptibility emerged in 1 isolate. Our findings require validation in future studies.

Disclosures
All authors: No reported disclosures.
2248. Clinical and Microbiological Outcomes Associated with Real-World Use of Ceftolozane/Tazobactam
Authors: Cabrera Nicolo , Tran Truc T , Miller William R , Dinh An Q , Hanson Blake , Munita Jose M , Shelburne Samuel A , Shelburne Samuel A , Aitken Samuel L , Aitken Samuel L , Garey Kevin W , Puzniak Laura A , Arias Cesar A 
Published: October 2019

Abstract

Background
Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor combination for treating Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T has been FDA-approved for complicated intra-abdominal and urinary tract infections and has just completed a trial in ventilator nosocomial pneumonia, but real-world outcome data are still emerging.

Methods
Demographic, microbiologic, treatment and outcome data of patients who received C/T for ≥48 hours from January 2016 to August 2018 at multiple centers within a single hospital system were retrospectively collected. Available isolates were analyzed for C/T susceptibility (by Etest) and whole-genome sequencing (WGS). Spades v.3.11.1 was used for assembly, multi-locus sequence typing v2.10 performed for in silico MLST with the PubMLST database and Abricate v0.7 was used for resistance gene screening with the CARD database.

Results
Among 45 patients, 58% were non-white, 53% were female and 13% were immunocompromised. The median age was 64 years (IQR, 50 to 69). At the time of the index event, a high proportion of patients required ICU care (42%) and pressor support (13%) as well as had invasive devices in place (64%). A minority (2.4%) had prior exposure to C/T. Respiratory infections were most common (38%) followed by urinary tract (20%). Concomitant Gram-negative agents were used in 18%. 69% achieved clinical success (i.e., recovery from infection-related signs and symptoms). The in-hospital mortality rate was 16% of which 5 out of 7 were attributed to infection. Microbiology was available for 91% of patients; 84% had PA isolates resistant to at least 3 antipseudomonal classes (Figures 1 and 2). Ten PA isolates were analyzed with WGS (Table 1). C/T resistance arose during therapy in one patient (MIC increase from 1 to 128 µg/mL). WGS showed a substitution in AmpC β-lactamase (A46D) and presence of blaCARB-2.

Conclusion
Although C/T was used in a critically ill population with highly resistant organisms, cure rates were high and mortality was low. Acquired β-lactamases were not frequently seen among the PA isolates. C/T is a vital therapeutic option, particularly on MDR isolates for which options are limited.

Disclosures
Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
2250. Combination Vancomycin Plus Cefazolin for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections
Authors: Jorgensen Sarah C J , Trinh Trang D , Zasowski Evan J , Alosaimy Sara , Melvin Sarah , Bhatia Sahil , Dhar Sorabh , Mynatt Ryan P , Pogue Jason M , Rybak Michael J 
Published: October 2019

Abstract

Background
Combination β-lactam and vancomycin (VAN) prevent the emergence of resistance and result in synergistic antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. We sought to provide clinical translation to these data and determine if patients with MRSA bloodstream infection (BSI) treated with VAN + cefazolin (VAN/CFZ) via our MRSA BSI clinical pathway had improved clinical outcomes compared VAN alone.

Methods
Multicenter, retrospective, comparative cohort study from 2006 to 2019 in adults with MRSA BSI treated with VAN for ≥ 72 hours. VAN/CFZ was defined as VAN + CFZ within ≤ 72 hours of index culture for ≥ 24 hours. Other β-lactams were allowed for < 48 h in the VAN/CFZ group. The VAN alone group could not have other β-lactams within 7 days of treatment initiation. The primary outcome was clinical failure defined as a composite of 30-d all-cause mortality, 60-day recurrence, and persistent BSI (≥ 7 days). The independent effect of VAN/CFZ on clinical failure was evaluated with multivariable logistic regression. The primary safety endpoint was nephrotoxicity within 7 days of treatment initiation.

Results
A total of 237 patients were included (104 VAN/CFZ, 133 VAN). The most common BSI sources were skin/soft tissue (29.1%), IV catheter (21.9%), osteoarticular (20.3%) and infective endocarditis (16.0%). Demographic and clinical characteristics were similar between groups except VAN/CFZ had a higher median APACHE II score (18 vs. 13, P = 0.011). VAN/CFZ patients were also more likely to have received an infectious disease consult (100% vs. 81.2%, P < 0.001). Median (IQR) duration of CFZ was 115 (87–164) hours. After controlling for age, APACHE II score, ID consult and infection source, VAN/CFZ was associated with reduced odds of clinical failure (aOR 0.425, 95% CI 0.228, 0.792). Bivariate outcomes are shown in the table:

Conclusion
Patients with MRSA BSI treated with VAN/CFZ vs. VAN experienced fewer clinical failures, supporting additional studies evaluating the role of adjuvant CFZ for MRSA BSI.

Disclosures
All authors: No reported disclosures.
2254. Multicenter Evaluation of Ceftazidime–Avibactam for Multidrug-Resistant Pseudomonas aeruginosa Infections
Authors: Jorgensen Sarah C J , Trinh Trang D , Zasowski Evan J , Alosaimy Sara , Lagnf Abdalhamid M , Bhatia Sahil , Melvin Sarah , Simon Samuel , Steed Molly E , Rosenberg Joshua R , Estrada Sandra J , Davis Susan L , Rybak Michael J 
Published: October 2019

Abstract

Background
Ceftazidime–avibactam (CZA) is a novel cephalosporin/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) and multidrug-resistant (MDR) Pseudomonas aeruginosa (PA). Real-world experience with CZA for CRE infections is accumulating but data on its use for MDR PA infections remains limited.

Methods
Retrospective, multicenter cohort study describing the clinical characteristics and outcomes of patients treated with CZA (≥ 72 hours) for MDR PA infections between 2015 and 2018.

Results
Fifty-one patients were included. The median (IQR) age was 61 (43, 71) years. Most patients had MDR risk factors including recent hospitalization (74.5%), recent antimicrobial exposure (84.3%), and/or previous infection or colonization with an MDR pathogen (58.8%). The median Charlson Comorbidity score was 4 (2, 6) and the median APACHE II score was 20 (12, 29). Infections were predominantly (68.6%) hospital-acquired and 52.9% of patients were in the ICU at infection onset. The common sources were respiratory tract (60.8%), osteoarticular (11.8%) and skin and soft tissue (11.8%). Two patients had positive blood cultures. PA antibiotic susceptibilities were as follows: ceftazidime 52.6% (n = 51), CZA 92.0% (n = 25), ciprofloxacin 10% (n = 30), meropenem 19.6% (n = 46), piperacillin–tazobactam 30.4% (n = 4) and tobramycin 72.9% (n = 48). Most (60.8%) infections were polymicrobial including 15 (29.4) CRE co-infections. CZA was started 97 (50, 170) hours after culture collection and continued for 9 (7, 14) days. Only 8 patients (15.7%) received active antibiotic therapy before CZA. Combination CZA therapy was used 35.3%, most often an aminoglycoside (8/18, 44.4%). Clinical cure or improvement was achieved in 40 patients (78.4%), and 42 (82.4%) were discharged alive. Among patients with repeat cultures (n = 11), CZA resistance development was not detected. Three patients (5.9%) experienced infection recurrence within 30 days of completing therapy.

Conclusion
The use of CZA was associated with high rates of favorable outcomes in complex patients with MDR PA infections. Future studies evaluating long-term outcomes and comparative studies are needed to more precisely define the role of CZA for MDR PA infections.

Disclosures
All authors: No reported disclosures.
2255. The Use of Dalbavancin for Staphylococcus aureus Bacteremia in Persons Who Inject Drugs (PWID)
Authors: Van Hise Nicholas W , Anderson Michael , McKinsey David , McKinsey Joel , Harting Brian , Belmares Jaime , Petrak Russell M 
Published: October 2019

Abstract

Background
Staphylococcus aureus is a significant cause of bacteremia and is associated with high morbidity and mortality rates. In patients with S. aureus bacteremia, studies have proven that intravenous antibiotics are needed for the entire course of therapy. For some groups of patients, specifically in persons who inject drugs (PWID), the long-term use of IV antibiotics is not safe or feasible. In this population, the current options would be obtaining intravenous access daily for antibiotic infusions, oral antibiotics, or being admitted to a facility that can monitor the patient. Data concerning the utilization of dalbavancin for the treatment of S. aureus bacteremia are limited.

Methods
This was a multicenter, retrospective case series of patients treated with four to six weekly doses of dalbavancin at 5 infusion centers in 3 states under the care of Metro Infectious Disease Consultant (MIDC) physicians between January 1 and December 31, 2018. All patients received intravenous therapy through a peripherally inserted catheter that was removed immediately after the infusion was completed. All patients were evaluated by an MIDC physician at the time of the initial dalbavancin dose, and weekly through their course of therapy. Cure was defined as negative blood cultures and no clinical evidence of persistent or relapsing infection. All patients completed their prescribed dosing and had phone follow-up to assess treatment efficacy at weeks 4, 8, 12, and 24.

Results
Twenty-one patients were included in the analysis. All patients began therapy for S. aureus bacteremia as inpatients and were transitioned to dalbavancin as outpatients. All patients received dalbavancin 1 g followed by 500 mg doses for at least 3 more weeks with an average of 4 weeks of therapy. Of the 21 patients, 16 were able to be contacted post therapy. Of the 16 patients, 2 patients were readmitted within the 6 month time frame for recurrent bacteremia related to intravenous drug usage. The remaining 14 patients remained disease free at the 6 month interval. No patients experienced a line related issue or C. difficile infection during the course of therapy.

Conclusion
Use of dalbavancin to treat S. aureus bacteremia infections resulted in clinical cure and markedly decreased healthcare costs.

Disclosures
All authors: No reported disclosures.
2271. Bacteremia Due to Multi-Drug-Resistant Organisms Is an Independent Risk Factor for Death Among Patients Supported by Extracorporeal Membrane Oxygenation (ECMO)
Authors: Rivosecchi Ryan , Sappington Penny , Clarke Lloyd , Clancy Cornelius J , Nguyen Minh-Hong 
Published: October 2019

Abstract

Background
ECMO is a type of life-support for patients with refractory respiratory and/or cardiac failure. Our objective was to determine the incidence, resistance patterns and risk factors for development of blood stream infections (BSI) in patients receiving ECMO therapy.

Methods
This was a retrospective cohort study of a single intensive care unit. All patients receiving ECMO therapy between 7/1/13 and 4/28/18 were evaluated. Multidrug-resistant (MDR) pathogens were defined as non-susceptible to ≥1 agent in ≥3 antimicrobial classes, and vancomycin-resistant Enterococcus (VRE).

Results
471 patients received ECMO, accounting for 4,739 ECMO days. Thirty-six patients (7.6%) had ≥1 episode of BSI; 47 episodes occurred, resulting in 10 events per 1,000 ECMO days. The most common organisms were Enterobacteriaceae (26%), 33% of which were MDR. Staphylococcus aureus (17%), coagulase-negative Staphylococcus (17%), Enterococcus faecium (11%) and Candida spp. (6%) were also identified. Overall, 20% of BSI were due to MDR bacteria. Median duration of BSI was significantly longer for infections due to VRE (8.5 days), than other organisms (1 day; P = 0.0006). Duration of ECMO (P < 0.0001), continuous renal replacement therapy (P = 0.01), units of blood transfused (P = 0.0001) and end-stage lung disease (ESLD) awaiting transplant (P = 0.004) were risk factors for BSI. Duration of ECMO, units of blood transfused and ESLD were independent risk factors for BSI. VV vs. VA-ECMO or central vs. peripheral cannulation were not significant risk factors. By logistic regression, MDR bacterial BSI was associated with longer duration of ECMO (P = 0.001) and number of units of blood transfused (P = 0.01). 1-year mortality after initiation of ECMO was 48%. Independent risk factors for 1-year mortality were age (P < 0.0001) and BSI due to MDR bacteria (P = 0.049).

Conclusion
The rate of BSIs during ECMO is relatively low, but these infections are commonly caused by MDR bacteria and associated with high 1-year mortality. Clinicians should consider empiric antibiotic coverage for MDR bacteria in patients with BSI on prolonged ECMO, and in patients on ECMO who received multiple blood transfusions. Since MDR bacterial BSI is an independent risk factor for mortality, future research on preventive strategies are warranted in high-risk ECMO cohorts.

Disclosures
All authors: No reported disclosures.
2290. Carbapenem vs. Piperacillin–tazobactam Definitive Therapy for Patients with Bloodstream Infections Due to Ceftriaxone Not Susceptible Escherichia coli or Klebsiella species
Authors: MacVane Shawn H , Bhalodi Amira A , Spafford Kyle , Humphries Romney , Oppermann Niels 
Published: October 2019

Abstract

Background
Definitive therapy with piperacillin–tazobactam (TZP) for ceftriaxone (CRO)-resistant E. coli or K. pneumoniae bloodstream infections (BSI) has been shown to be inferior to carbapenem therapy in a randomized trial.

Methods
The Premier US database was queried for hospitalized patients with monomicrobial E. coli or Klebsiella spp BSI that were not susceptible (NS) to CRO between June 2015 and May 2018. Adults with index positive blood culture(s) drawn within the first 2 hospital days who were treated with active antibiotic therapy that continued for ≥3 consecutive days were included. We defined antibiotics administered on or prior to Day 3 as empirical therapy and all subsequent days as definitive therapy. Outcomes among patients who received definitive therapy with a carbapenem vs. TZP were evaluated.

Results
There were 954 patients (mean age, 67.6 years; 52.4% women) who met selection criteria and received active empirical therapy. 729/954 received carbapenem definitive therapy and 38/954 received TZP definitive therapy. Median Charlson Comorbidity Index scores were similar between carbapenem and TZP definitive therapy groups (6 vs. 5, P = 0.78). Crude 14-day in-hospital mortality for CRO-NS BSI due to E. coli or Klebsiella spp. was 4.4%. Definitive therapy with TZP (6/38; 15.8%) was associated with an increased likelihood of 14-day mortality relative to that of a carbapenem (22/729; 3.0%; P < 0.0001). The increased 14-day mortality observation was consistent in a multivariate cox proportional hazards model (adjusted hazard ratio, 5.70; 95% CI, 2.09 to 13.23; P = 0.002). Of patients who received carbapenem definitive therapy, 14-day mortality was 2.7% (19/693) if a carbapenem was part of empirical therapy and 8.3% (3/36; P = 0.06) if empirical therapy did not include a carbapenem. Median post-blood culture length of stay (7 vs. 6 days, P = 0.65) and hospital costs ($13,886 vs. $13,559, P = 0.62) were similar between carbapenem and TZP definitive therapy groups<./p>

Conclusion
In this large US database, definitive therapy with TZP was associated with an increased likelihood of 14-day mortality relative to that of definitive carbapenem therapy in patients with CRO-NS BSI due to E. coli or Klebsiella spp. These findings support recent clinical evidence in favor of definitive carbapenem therapy for CRO-NS BSI due to E. coli or Klebsiella spp.

Disclosures
All authors: No reported disclosures.
2291. Evaluation of Multidrug-Resistant Pseudomonas aeruginosa Isolates in Patients Receiving Ceftolozane/tazobactam
Authors: Bodo Emily C , Caffrey Aisling , Lopes Vrishali , Cusumano Jaclyn A , Puzniak Laura A , McCann Eilish , LaPlante Kerry 
Published: October 2019

Abstract

Background
Multidrug-resistant (MDR) Pseudomonas aeruginosa is a challenging pathogen to treat. Ceftolozane/tazobactam (C/T) is a combination cephalosporin and β-lactamase inhibitor that has demonstrated activity against MDR P. aeruginosa, including carbapenem-resistant isolates. The objective of this study was to evaluate multidrug resistance in P. aeruginosa isolates obtained from patients treated with C/T across the Veterans Affairs (VA) Healthcare System nationally.

Methods
Hospitalized patients who received at least 1 dose of CT between January 2015 and April 2018 and had a positive P. aeruginosa culture were included in this retrospective study. Culture source and antimicrobial susceptibility reports were assessed for each P. aeruginosa isolate. Isolates were categorized as multidrug-resistant based on the Centers for Disease Control (CDC) definition. Resistance rates were categorized by source of culture.

Results
We identified 174 positive P. aeruginosa cultures among 154 patients who received at least one dose of C/T during the study period. The most common sources of isolates were lung (40% of patients), urine (21%), skin and soft tissue (15%), blood (14%), and bone/joint (14%). Most patients (98.1%) had isolates that were MDR, with high rates of carbapenem (84.4%), extended-spectrum cephalosporin (82.5%), and fluoroquinolone (79.9%) resistance. In this cohort, 50.6% of patients received at least one antibiotic prior to initiating C/T to which their clinical culture was not susceptible.

Conclusion
Antibiotic resistance was high in this cohort of patients with P. aeruginosa, and as a result, use of non-susceptible antibiotics occurred in 50.6% of patients before C/T was started. The high carbapenem resistance rates are of great clinical concern, but highlight an area of utilization for C/T given its activity against carbapenem-resistant P. aeruginosa.

Disclosures
All authors: No reported disclosures.
2299. A London Hospital’s Experience of Confirmed Measles Infections and Re-Infections Between 2009 and 2019
Authors: Sturdy Ann , Haque Tanzina , Griffiths Paul , Brown Kevin , Irish Dianne , Mahungu Tabitha 
Published: October 2019

Abstract

Background
2018 to 2019 has seen a global resurgence in measles cases, with the UK seeing an over 3-fold increase in cases in 2018 compared with 2017. In this context, our center saw a cluster of geographically linked measles cases presenting in the first quarter of 2019. We present this with comparative data of confirmed measles cases from our center over the preceding 10 years. Given the growing recognition of measles “re-infection” in fully vaccinated individuals, we also present our first confirmed cases of reinfection within this cohort.

Methods
Retrospective analysis of confirmed measles cases (positive Measles IgM or detectable Measles RNA) between 2009 and 2019. Laboratory and demographic data were obtained from electronic patient records.

Results
18 cases (of which 14 were adults) of measles (all genotype D8 of those tested) were confirmed in the first 4 months of 2019. 12 presented within a 14 day period from a geographically linked part of North London. There were 4 confirmed measles re-infections (detectable measles RNA on a buccal swab with either a high Measles IgG avidity or previous documented measles immunity). From the 10 year data, cases peaked in 2011 and 2016 consistent with national trends. Of the 89 cases identified, 60 (67%) were adults, who were over twice as likely to be admitted as children, had a longer median length of stay in hospital (2 days vs. 1.5 days) and were more likely to develop a hepatitis (1/10 pediatric cases vs. 26/48 adults, p ≤ 0.01)or other complications. The majority of adults (68%) were unsure of their vaccination status.

Conclusion
4 cases of 18 in the first 4 months of 2019 were confirmed re-infections. Re-infections in fully vaccinated individuals are described in the literature, typically presenting with a milder course; however, these are the first cases we have identified at our center. Overall, adult cases were more likely to be admitted to hospital and to have a complicated course compared with children. Vaccination history in adults was of limited clinical utility due to lack of reliable documentation and the potential for reinfection.

Disclosures
All authors: No reported disclosures.