bluuebunny/crossref_metadata_2025_split huggingface dataset:
437. Gram-Negative Rod Skin and Soft-tissue infections following Breast Tissue Expander Surgery in Breast Cancer Patients
Authors: Hee Katzman Ju , Aslam Sadaf , Pate Donna Mae M , Guidish Nicole , Power Shelby , Maravilla Clarissa , Perkins Janelle , Greene John 
Published: October 2019

Abstract

Background
Breast cancer patients who undergo tissue expander surgery (TES) are at an increased risk of developing gram-negative rod (GNR) skin and soft-tissue infection (SSIs) and its complications including prolonged antibiotic therapy, antibiotics side effects, and implant removal. Current perioperative antimicrobials focus mostly on gram-positive organisms, but the presence of a foreign body increases the risk of GNR SSI. We describe here the most common GNR bacteria and their susceptibility patterns that cause SSI after TES among breast cancer patients.

Methods
We conducted a retrospective cohort study at Moffitt Cancer Center, Tampa, FL from January 2016, to January 2018, on all breast cancer patients who developed GNR SSIs following TES. We reviewed records after approval from the Institutional Review Board. The data collected included patient’s age, pathogens from wound culture, antibiotic susceptibilities, the perioperative and definitive antibiotics used.

Results
A total of 38 cases of GNR SSI with a mean age of 56 ± 11 years were identified. The 3 most common pathogens were Pseudomonas aeruginosa (45%), Serratia marcescens (16%), and Klebsiella pneumoniae (8%) (Figure 1). The susceptibility pattern was available for 33 cases. Pseudomonas and Klebsiella isolates were susceptible to all tested antibiotics (Table 1). The Stenotrophomonas isolates showed resistance to ceftazidime. Enterobacter cloacae, Enterobacter aerogenes, Morganella morganii, and Acinetobacter baumannii complex, showed resistance to cefazolin. Twenty-five cases (74%) received perioperative antibiotics for gram-positive organisms; mostly cefazolin, and vancomycin. The common antibiotics used for definitive treatment were ciprofloxacin, cefepime, ceftazidime, piperacillin–tazobactam, and meropenem.

Conclusion
In centers with a high percentage of GNR SSI following TES should consider using perioperative antibiotics that include coverage against Pseudomonas aeruginosa, the most common isolate (45%). The use only of cefazolin or other antibiotics against gram-positive organism may be inadequate. However, GNR infection may occur from 48 hours to 2 weeks postoperatively and may be from the acquisition of the GNR at home in which perioperative antibiotics may have minimal effect.

Disclosures
All authors: No reported disclosures.
447. Disease Progression in Patients with Acute Bacterial Skin and Skin Structure Infections: A Comparative Analysis Between Oritavancin and Vancomycin
Authors: Whittaker Cristen A , Nhan Ethan , Nguyen Hien , Trivedi Manish , Reilly Joseph 
Published: October 2019

Abstract

Background
Without the appropriate treatment, acute bacterial skin and skin structure infections (ABSSSI) have the potential to progress to more serious infections such as bacteremia and osteomyelitis. Utilizing single-dose oritavancin rather than vancomycin with step-down oral antibiotics, the need for compliance with outpatient antibiotics is eliminated. The objective of this study was to determine whether oritavancin use may reduce the sequelae from ABSSSI treatment failures, prevent skin infection recurrences, and subsequently improve patient outcomes.

Methods
Patients administered oritavancin or vancomycin for treatment of ABSSSI between May 2017 and March 2019 were included in this retrospective evaluation. The primary endpoint was to determine the 30-day ABSSSI progression rate to bacteremia, osteomyelitis, or endocarditis between treatment arms based on hospital readmissions. Study investigators determined that the source of each resultant infection was from the initial ABSSSI based on the presence of their prior skin infection and cultures, as well as history of present illness and reported patient compliance. In cases of osteomyelitis, infection location was also considered. The secondary endpoint was to determine the ABSSSI readmission rates between treatment arms. Data were analyzed by fisher’s exact test, chi-square test or t-test as appropriate.

Results
A total of 99 patients receiving oritavancin and 100 patients receiving vancomycin with prescribed step-down oral antibiotics were identified as meeting inclusion criteria. Eighteen of 100 patients (18%) returned for recurrent ABSSSI infection in the vancomycin arm while 7 of 99 (7.1%) returned in the oritavancin arm (P = 0.0309). Of the 7 returning oritavancin patients, 1 (14.3%) had bacteremia as a result of persistent ABSSSI compared with 7 of 18 (38.9%) patients who previously received vancomycin returned with bacteremia, including 1 case of osteomyelitis (P = 0.0649).

Conclusion
Utilizing oritavancin for treatment of ABSSSI in this population resulted in improved patient outcomes, significantly fewer hospital readmissions for ABSSSI, and decreased infection sequelae from inadequately treated skin infections.

Disclosures
All authors: No reported disclosures.
448. Impact of Doxycycline Prophylaxis on Skin and Soft-Tissue Infection Incidence in Naval Special Warfare Trainees
Authors: Smith Alfred G , Schwartz Julia , Burger Sara , Tilley Drake H , Maves Ryan C 
Published: October 2019

Abstract

Background
Skin and soft-tissue infections (SSTIs) are a common complication of military training. Naval Special Warfare (NSW) training requires prolonged periods of extreme physical exertion and unique environmental exposures, including extended immersion in ocean water. A centerpiece of SEAL training is referred to as “Hell Week” (HW), a colloquial term to reflect the intense physical obstacles and exposure to extreme environmental conditions endured by candidates. Due to such environmental exposures, NSW trainees are at increased risk for SSTI due to uncommon organisms. A prior outbreak of Shewanella SSTI and bacteremia among NSW trainees led to the initiation of prophylactic doxycycline 100 mg daily during and for 7 days after HW to attempt to reduce this risk. The efficacy of this intervention is undetermined.

Methods
Doxycycline prophylaxis was initiated in August 2015. We conducted a retrospective analysis of SSTI incidence presenting for medical attention among NSW trainees from April 2013 to November 2018, using case records collected prospectively at the Naval Special Warfare Center. The incidence of SSTI was calculated based on the size of a given class and the number of affected trainees. SSTI cases were then divided and analyzed as occurring during vs. after HW.

Results
The pre-intervention cohort consisted of 1626 NSW trainees. A total of 76 trainees developed SSTI, with 20 cases during HW and 56 cases in the post-HW period. In the post-intervention cohort, 2022 trainees experienced a total of 81 cases of SSTI during HW and 83 in the post-HW period. 45% of all SSTI cases occurred in the months of June, July, and August. The incidence of cellulitis between the pre- and post-intervention cohorts during HW was 2% and 4%, respectively, and 5% and 6.4% in the post-HW period. There were no hospitalizations for invasive gram-negative infections following the initiation of doxycycline prophylaxis.

Conclusion
Doxycycline prophylaxis does not appear to reduce the incidence of SSTI but may reduce the incidence of certain severe infections. The choice of antibiotic prophylaxis and dosing may require further investigation. Seasonality of SSTI among NSW trainees is an unexpected finding and may provide valuable information for the prevention of future illness.

Disclosures
All authors: No reported disclosures.
450. Evaluation of Linezolid Pharmacokinetics in Obese Patients with Severe Skin and Soft-Tissue Infections
Authors: Blackman Alison L , Jarugula Praneeth , Nicolau David P , Ho Chui Sai , Joshi Manjari , Gopalakrishnan Mathangi , Heil Emily 
Published: October 2019

Abstract

Background
Linezolid is an oxazolidinone antibiotic with broad activity against Gram-positive bacteria and serves as an option for treating severe skin and soft-tissue infections (SSTIs). Adult FDA-labeled dosing is fixed at 600 mg IV/PO twice daily. Although conflicting, current literature is suggestive that critically ill, obese patients require increased doses. Based on this literature, our institutional guidelines recommend linezolid 600 mg every 8 hours for patients ≥150 kg. This study aimed to determine whether obese patients receiving linezolid for severe SSTI attain pharmacokinetic/pharmacodynamic (PK/PD) targets.

Methods
Adult patients with a body mass index (BMI) ≥30 who were hospitalized and receiving IV linezolid were eligible for consent in this prospective cohort study. A severe SSTI was defined by one of the following: necrotizing fasciitis, myonecrosis, or SSTI with sepsis based on qSOFA score or SIRs criteria. Four blood samples were collected at steady state, after at least 3 linezolid doses, at 2, 4, and 6 hours after the dose and as a trough before the next dose. Linezolid serum concentrations were determined by HPLC. Non-compartmental methods in Phoenix-WinNonlin (Version 6.4) were used to estimate individual PK parameters. The PK parameters were used to determine the concentration-time profile assuming one-compartment kinetics. Target attainment was defined as achieving a 24-hour area under the curve (AUC0–24)/minimum inhibitory concentration (MIC) ≥100 or time above the MIC ≥ 85%.

Results
Eleven patients were included in the study. The median BMI was 45.7 (34.6–72.7) and median total body weight was 141.3 kg (99.9–188). Necrotizing fasciitis was the most common SSTI type at 45.5%. Four patients received linezolid 600 mg every 8 hours, 3 patients of which were ≥150 kg. Two patients received renal replacement therapy at the time levels were drawn. Based on non-compartmental analysis, the mean AUC0–24 was 208.1 hr*mg/L (± 85.3). All but one patient, who grew E. faecalis with a MIC of 2, met PK/PD targets based on AUC/MIC ≥100. All patients achieved concentrations above MIC for 100% of the dosing interval.

Conclusion
All patients met defined PK/PD targets with linezolid doses received. This study validates current institutional dosing guidelines for patients with severe SSTIs.

Disclosures
All authors: No reported disclosures.
463. Evaluation of Trimethoprim-Sulfamethoxazole Utilization for Skin and Soft-Tissue Infections During Emergency Department Visits at Two Community Teaching Hospitals
Authors: King Esther , Patel Dimple , Roland Robert , Kessler Jason , Saini Amar , Jindal Nimit 
Published: October 2019

Abstract

Background
Increasing trimethoprim/sulfamethoxazole (TMP/SMX) resistance has been noted among inpatient and outpatient isolates of methicillin-resistant S. aureus (MRSA) at two community teaching hospitals in Northern New Jersey. The purpose of the study is to evaluate the indications for TMP/SMX prescriptions for adult Emergency Department (ED) discharges. In addition, since IDSA guidelines for the management of skin and soft-tissue infections (SSTIs) do not recommend the use of anti-MRSA antibiotics for non-purulent SSTIs, we chose to determine guideline concordance of antibiotic selection for non-purulent SSTIs.

Methods
TMP/SMX susceptibility data for S. aureus from 2014 to 2018 at two community teaching hospitals were compiled. A retrospective chart review was then conducted of all adult patients who were discharged from the ED with an antibiotic prescription from January to March 2019. Antibiotic indications were extracted based on ED diagnosis and review of the medical record. In patients treated for non-purulent cellulitis, antibiotic prescription information and antibiotic allergies were collected and assessed for guideline concordance. Guideline-concordance for non-purulent cellulitis was defined as treatment with B-lactams or clindamycin.

Results
TMP/SMX susceptibility against S. aureus is displayed in Figure 1. Of 338 patients discharged with a prescription for TMP/SMX, 60% were treated for SSTIs, 30% were treated for urinary tract infections, and 10% were treated for other indications. Among 203 patients treated with a TMP/SMX-containing regimen for SSTIs, 76% had purulent or wound-related infection. Of 137 patients treated for non-purulent cellulitis, 68% of antibiotic regimens were guideline-concordant. In addition, 19% of antibiotic regimens for non-purulent cellulitis contained TMP/SMX.

Conclusion
A substantial reduction in TMP/SMX susceptibility among MRSA, but not MSSA, isolates has been observed. Opportunities to improve utilization of TMP/SMX for SSTIs exist at our institutions. Additional studies are warranted to determine the factors associated with increasing TMP/SMX resistance in MRSA.

Disclosures
All authors: No reported disclosures.
471. Safety and Efficacy of Oral and/or Intravenous Tedizolid Phosphate (TZD) in Adolescents with Acute Bacterial Skin and Skin Structure Tissue Infections (ABSSSI)
Authors: Bradley John S , Antadze Tinatin , Mitha Ismail H , Ninov Borislav , Tayob Mohammed S , Broyde Natasha , Butterton Joan R , Chou Margaret Z , De Anda Carisa S , Kim Jason Y , Sears Pamela S 
Published: October 2019

Abstract

Background
Tedizolid phosphate has activity against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, and was approved for the treatment of ABSSSI in adults in 2014. This study compared the safety and efficacy of TZD with protocol-specified, active comparators for the treatment of ABSSSI in adolescents.

Methods
This was a randomized, assessor-blind, global, multicenter, phase 3 study of TZD vs. active comparator for the treatment of gram-positive ABSSSI in adolescents (aged 12 to < 18 years; NCT02276482). Enrolled patients were stratified by region and randomized 3:1 to TZD 200 mg (IV and/or oral) once daily for 6 days or investigator-selected active comparator per local standard of care (IV vancomycin, linezolid, clindamycin, flucloxacillin, or cefazolin, and/or oral linezolid, clindamycin, flucloxacillin, or cephalexin) for 10 days. The primary endpoint was safety. The percentages of patients with treatment-emergent adverse events (TEAEs) were documented; secondary efficacy endpoints included the blinded investigator’s assessment of clinical success at a test of cure visit (18–25 days after start of dosing) and early clinical response (≥20% reduction from baseline lesion area) at 48–72 h. No hypothesis testing was planned for the treatment groups.

Results
Of the 121 patients enrolled, 120 were treated (TZD, N = 91; comparator, N = 29). Median (range) age was 15 (12–17) years. Most patients were male (62.5%), white (86.7%), and enrolled in Europe (78.3%). Infections included major cutaneous abscess (42.5%), cellulitis/erysipelas (40.0%), and infected wound (17.5%). At baseline, the median (range) lesion surface area was 82.1 (14–978) cm2. Of those with gram-positive cultures (n = 64), S. aureus was most frequently isolated (n = 55 [85.9%]) with 3 isolates (4.7%) being methicillin resistant. TZD was well tolerated, and TEAEs were balanced between treatment arms (TZD, 14.3%; comparator, 10.3%). A total of 3 (3.3%) patients in the TZD group and 1 (3.4%) in the comparator group experienced a single-drug-related TEAE. Clinical success rates were high and similar between treatment groups (table).

Conclusion
TZD demonstrated comparable safety and efficacy to comparator in the treatment of ABSSSI in adolescents.

Disclosures
All authors: No reported disclosures.
478. Outcomes of Extended-Spectrum β-Lactamase-Producing Escherichia coli Bloodstream Infection in Neutropenic Patients with Hematological Malignancies
Authors: Aslam Sadaf , Denham James , Greene John 
Published: October 2019

Abstract

Background
Infections with extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae is an emerging problem leading to poor clinical outcomes and increased mortality. The purpose of this study was to determine the prevalence, risk factors and outcomes of ESBL-producing E. coli (EC) in bloodstream infections (BSIs) of neutropenic patients with hematological malignancies and compare the difference with Non-ESBL producing EC.

Methods
Through an IRB approved protocol, a retrospective cohort study was conducted at the H. Lee Moffitt Cancer Center from January, 2007 till October, 2017. Of the 310 records, who had +ive blood cultures for E. Coli, a total of 63 neutropenic patients with hematological malignancies were identified based on the bloodstream infections with ESBL-EC and Non ESBL EC. Data included demographics, underlying malignancy, type of bone marrow transplant, duration of neutropenia, antibiotics use pre and post culture, length of hospital stay, severity of infection, ventilator use, and mortality data.

Results
A total of 310 cases with hematological malignancy and neutropenia were reviewed, 63 were identified as +ive blood culture for E. coli. Out of the 63 cases, 17 were ESBL-EC +ive and 46 were non-ESBL-EC. The prevalence of ESBL-EC was highest in the year 2015 (29.4%) and decreased in the subsequent years (Figure 1). The mean ages of the two groups were 53.59 ±12.4 and 60.82 ± 11.1, respectively. The average length of stay for the ESBL-EC group was 26.59 ± 11.2 days, longer than the non-ESBL EC group 21.96 ± 11.2. Days of neutropenia in non-ESBL vs. ESBL EC were 9 days ± 8.3, and 19 days ± 22.0, respectively, P < 0.01). No differences were observed in the 30–60 day mortality and other outcomes listed in Table 1.

Conclusion
The prevalence of ESBL-EC was observed to be higher in patients who were neutropenic for longer duration, were older and resulted in longer hospital stay. Early identification and empirical therapy in neutropenic patients suspected to have ESBL-EC infection is crucial. Also, the infection with ESBL-EC was higher in the year 2015 and decreased in the subsequent years. After higher rates, perhaps infection control, lab reporting changes, antibiotic stewardship and transmission-based precautions might have played a role.

Disclosures
All authors: No reported disclosures.
481. Evolution of Carbapenem-Resistant Pseudomonas aeruginosa (CR-PA) Genetic Lineages and Acquisition of β-Lactamase Enzymes
Authors: Sakurai Aki , Dinh An Q , Hanson Blake , Shropshire William C , Tran Truc T , Wanger Audrey , Arias Cesar A , Miller William R 
Published: October 2019

Abstract

Background
Nosocomial infections due to CR-PA are associated with significant morbidity and mortality, and knowledge of epidemiology and underlying mechanisms of antimicrobial resistance is critical to addressing this threat. Recently, we identified a CR-PA of sequence type (ST) 309 resistant to all available β-lactams due to acquired β-lactamases as a potential emerging clone. To assess the evolving landscape of resistance in CR-PA we performed a cross-sectional survey of historical and contemporary isolates utilizing phenotypic testing and whole-genome sequencing (WGS).

Methods
Historical CR-PA isolates (n = 61, collected from 1999 to 2015) and contemporary isolates (n = 110, collected from 2017 to 2018) from a large urban hospital network in Houston, TX were tested for susceptibility to meropenem, aztreonam (ATM), ceftolozane/tazobactam (C/T), and ceftazidime/avibactam (CZA) using E-test on Mueller–Hinton (MH) agar. WGS for all isolates was performed on a MiSeq platform (Illumina). Data analysis was performed using a custom analysis pipeline, including Tseemann MLST tool, Resfinder, and Abricate using the CARD database.

Results
The prevalence of resistance across all β-lactams tested increased in contemporary strains as compared with that of historical strains (Figure 1). Among important contemporary antipseudomonal antibiotics C/T, ATM, and CZA, resistance increased from 0%, 22%, and 5% to 15%, 44%, and 16%, respectively (Figure 1). WGS revealed that ST235 was the most common sequence type, followed by ST111 in the historical collection (Figure 2). In contrast, a larger degree of genetic diversity was found in contemporary isolates, with the emergence of multidrug-resistant clones such as ST308 (2%) and ST309 (3%). Resistance to C/T was associated with acquired β-lactamases in 88% (14/16) of isolates, including VIM-2, GES-19/GES-26, VEB-1, NMD-1, and OXA enzymes.

Conclusion
Resistance to newer agents C/T and CZA markedly increased in contemporary CR-PA strains. While the epidemic clones ST235 and ST111 were the most frequent STs, ST308 and 309 have emerged among contemporary MDR isolates. Most concerning was the association of C/T resistance and the acquisition of β-lactamases, due to the potential for further dissemination.

Disclosures
All authors: No reported disclosures.
486. Epidemiology of Carbapenem-Resistant Pseudomonas aeruginosa Identified through the Emerging Infections Program (EIP), United States, 2016–2018
Authors: Grass Julian E , Bulens Sandra N , Bamberg Wendy M , Janelle Sarah J , Schutz Kyle , Jacob Jesse T , Bower Chris W , Blakney Rebekah , Wilson Lucy E , Vaeth Elisabeth , Li Linda , Lynfield Ruth , Snippes Vagnone Paula , Dobbins Ginette , Phipps Erin C , Hancock Emily B , Dumyati Ghinwa , Tsay Rebecca , Cassidy P Maureen , West Nicole , Kainer Marion A , Mounsey Jacquelyn , Stanton Richard A , McAllister Gillian A , Campbell Davina , Lutgring Joseph D , Karlsson Maria , Walters Maroya S 
Published: October 2019

Abstract

Background
Pseudomonas aeruginosa is intrinsically resistant to many commonly used antimicrobials, and carbapenems are often required to treat infections. We describe the crude incidence, epidemiology, and molecular characteristics of carbapenem-resistant P. aeruginosa (CRPA) in the EIP catchment area.

Methods
From August 1, 2016 through July 31, 2018, we conducted laboratory- and population-based surveillance for CRPA in selected areas in eight sites. We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period. Patient charts were reviewed. Analysis excluded cystic fibrosis patients. A random sample of isolates was collected. Real-time PCR to detect carbapenemase genes and whole-genome sequencing are in progress.

Results
We identified 4,209 cases in 3373 patients. The annual incidence was 14.50 (95% CI, 14.07–14.94) per 100,000 persons and varied among sites from 4.89 in OR to 25.21 in NY. The median age of patients was 66 years (range: < 1–101), 42.1% were female, and nearly all (97.5%) had an underlying condition. Most cases were identified from urine (42.8%) and lower respiratory tract (35.7%) cultures. Nearly all (93.3%) occurred in patients with inpatient healthcare facility stay, surgery, chronic dialysis, or indwelling devices in the prior year; death occurred in 7.2%. Among 937 isolates tested, 847 (90.4%) underwent PCR; six (0.7%) harbored a carbapenemase, from four sites (CO, MD, NY, and OR): blaVIM (3), blaKPC (2), and blaIMP (1). Of 612 (65.3%) isolates sequenced, the most common ST types were ST235 (9.2%) and ST298 (4.9%).

Conclusion
Carbapenemases were rarely the cause of carbapenem resistance but were found at EIP sites with high and low CRPA incidence. The emergence of mobile carbapenemases in P. aeruginosa has the potential to increase the incidence of CRPA. Increased detection and early response to carbapenemase-producing CRPA is key to prevent further emergence.

Disclosures
All authors: No reported disclosures.