bluuebunny/crossref_metadata_2025 huggingface dataset:
422. Pooling Strategy for Chlamydia trachomatis and Neisseria gonorrhoeae Reduces Cost of GeneXpert Molecular STI Screening in Two Limited-Resource Clinics in Zambia
Authors: Connolly Sarah , Kilembe William , Inambao Mubiana , Visoiu Ana-Maria , Sharkey Tyronza , Parker Rachel , Hunter Eric , Allen Susan
Published: October 2019

Background

Risk of heterosexual HIV-1 transmission is elevated in the presence of sexually transmitted infections (STIs) such as chlamydia (CT) and gonorrhea (NG). Syndromic management is a common, low-resource, approach to detecting STIs. However, CT and/or NG infections in women are often asymptomatic and therefore missed by syndromic management. Molecular testing for STIs is highly sensitive, but time and cost restraints preclude implementation of these technologies in resource-limited settings. Pooling samples for testing together in GeneXpert cartridges is one strategy for reducing the cost per individual tested.

Methods

This project describes the development of a pooling strategy based on social and demographic factors associated with CT/NG prevalence rates in a cohort of high-risk women in Zambia. Logistic regression modeling was used to predict the probability of a positive CT/NG test result in the presence of various factors. Data from a 2016 cross-sectional sub-study on intra-vaginal practices in 509 women was examined and an easy-to-use diagnostic screening checklist was created to categorize women by probability of testing positive on the GeneXpert. An algorithm considering cost of each test and prevalence of disease in each group determined the optimal pool size for each risk category.

Results

Logistic regression identified CT/NG to be associated with: city, age, education, long-acting reversible contraception usage, and laboratory results for bacterial vaginosis, Trichomonas vaginalis, and incident syphilis on the day of CT/NG testing. Signs and symptoms were not found to be associated. The overall prevalence of either CT and/or NG infection in this population was 17%. Low, middle, and high-risk groups could be separated based on checklist score with 7.52%, 18.30%, and 46.51% CT/NG prevalence, respectively.

Conclusion

Pooling women with similar CT/NG predictive factors together, or testing those at highest risk individually, reduces the cost per test. Further implementation of this tool to guide presumptive treatment, in lieu of molecular testing, increases the cost-saving potential. The strategies described in this study are applicable to other low-resource clinical settings seeking to provide the accuracy of molecular testing with a reduced financial burden.

Disclosures

All authors: No reported disclosures.
425. Longitudinal Trends in Risk Behaviors and Sexually Transmitted Diseases among Adolescents and Young Adults at a Sexually Transmitted Diseases Clinic, 2013–2017
Authors: Rusley Jack , Tao Jun , Koinis-Mitchell Daphne , Rosenthal Alex , Montgomery Madeline , Nunez Hector R , Chan Philip , Chan Philip
Published: October 2019

Background

Sexually transmitted disease (STD) rates continue to rise in the United States (US). Over half of all new STDs occur in adolescents and young adults (AYA). Few studies have evaluated how sexual behaviors such as number of partners or condom use may contribute to this increase. We aimed to determine the association of sexual behaviors and condom use with STD incidence over time among AYA.

Methods

We reviewed all AYA ages 13–26 years attending a public STD clinic in Rhode Island from 2013–2017. We reviewed demographic and behavioral data including age, gender identity, risk group, race, ethnicity, insurance status, sexual behaviors, substance use, self-reported STD/HIV diagnosis (lifetime, past year), condom use, and HIV/STD testing results. We report proportions in 2013 and 2017, and performed trend analyses (Cocharn-Armitage test for categorical variables and Kruskal–Wallis trend test for continuous variables) to determine trends over time.

Results

A total of 3,822 AYA visited the clinic during the study time period. An increasing trend was observed for: multiple (≥5) partners (29% of AYA in 2013 vs. 38% in 2017, P < 0.001), self-reported past year and lifetime STD diagnosis (12 vs. 21%, P < 0.001 and 19 vs. 33%, P < 0.001, respectively), and lab-documented diagnosis of any STD (15 vs. 25%, P < 0.001), syphilis (2 vs. 5%, P = 0.006), any chlamydia (11 vs. 20%, P = 0.001), and any gonorrhea (3 vs. 8%, P = 0.008). A decreasing trend was observed for: white race (66% in 2013 vs. 43% in 2017, P < 0.001), uninsured (73 vs. 53%, P < 0.001), condomless sex during oral as well as vaginal/anal sex (22 vs. 10%, P = 0.001 and 16 vs. 8%, P = 0.001, respectively), and self-reported HIV diagnosis (2.5% to 0.9%, P = 0.016).

Conclusion

Among AYA, risk behaviors such as condomless sex and multiple partners increased significantly from 2013–2017, which may be contributing to an increase in STDs. Increased public health efforts are needed to promote education and other interventions to address behaviors associated with STD transmission.

Disclosures

All authors: No reported disclosures.
435. Iliopsoas Abscess in Egyptian Patients Presenting to Cairo University Hospitals
Authors: Elanany Mervat , Abdel Mageed Reham , Hasaballah Maha
Published: October 2019

Background

The incidence of iliopsoas abscess (IPA) is rare but the frequency of this diagnosis has increased with the use of ultrasonography and computed tomography (CT). The vague presentation leads to delays in diagnosis and increases morbidity. Managing iliopsoas abscess is still forming a therapeutic challenge. The aim of this research was to study the features of iliopsoas abscess cases including the etiology and clinical presentation.

Methods

Patients and Methods. all patients presented to the orthopedic outpatient clinic (Cairo university hospitals) by back pain were screened by plain X-ray and IPA was by ultrasonography (US). The confirmed patients were diagnosed as having psoas or iliopsoas collection and subjected to: full history taking, full laboratory workup, screening for tuberculosis, radiological studies and ultrasound-guided needle aspiration of the abscess. The aspirate samples were microbiologically tested by culture (aerobic, anaerobic and MGIT) and PCR technique. Follow-up US was done within 7 days from the first aspiration.

Results

The outpatient clinic received 40 thousand back pain cases during a one-year study. Only 14 patients were diagnosed as IPA. The age ranged 19–65years (mean 37years) and 57% were male. 44.4% patients had primary IPA while 55.5% patients had secondary IPA. All patients had limping and flank pain, backache or both. Fever was common 90% of patients. Leukocytosis was found in 55.5% of patients, ESR was elevated and CRP was positive in all patients. Z.N stain for AFB was negative in all patients. Culture of aspirated fluid revealed S.aureus as the commonest organism (44% of cultures), then E.coli in (22% of cultures), Mycobacterial tuberculosis in 7% by MGIT culture and PCR. Other cultures were negative. All patients were treated by drainage and appropriate antibiotics. surgical intervention was needed in 22% patients. Recurrence occurred in only 1 patient with tuberculous iliopsoas abscess.

Conclusion

Although IPA is rare, the appropriate diagnosis by US is needed. S.aureus is the commonest pathogen but Mycobacterial tuberculosis could be a cause for recurrence.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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

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

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.
487. Prevalence of Antimicrobial Resistance in Gram-Negative Bacilli Bloodstream Infections at a Tertiary Teaching Hospital in the Dominican Republic
Authors: Mena Lora Alfredo J , Rodriguez Abreu Julia , Blanco Claudia , de Lara Jacquelin , Bleasdale Susan C
Published: October 2019

Background

Bloodstream infections (BSI) with gram-negative bacilli (GNB) are a major cause of morbidity and mortality worldwide. Sepsis due to BSI can carry a mortality rate as high as 40%, with higher mortality in developing nations. Early and appropriate empiric therapeutic selection plays an important role in survival. The rising incidence of antimicrobial resistance (AMR) limits empiric treatment options. Local susceptibility patterns can vary per region, institution or setting. Understanding local AMR may help guide empiric treatment choices. We seek to describe resistance rates for GNB BSI in the Dominican Republic (DR).

Methods

This is a retrospective review of antimicrobial susceptibility patterns from bloodstream infections in a tertiary hospital in the DR. Susceptibility data from all adult inpatient blood cultures were collected from January 1 to December 31, 2017.

Results

A total of 124 blood cultures were reported. The most common organisms were Escherichia coli (43%) and Klebsiella pneumoniae (23%). Fluoroquinolone resistance was present in 70% of E. coli. Phenotypic susceptibility patterns consistent with extended-spectrum β-lactamase (ESBL) producing GNB were present in 46% of isolates. Carbapenem resistance was found in 4 samples and was most common in P. aeruginosa. Susceptibility profile is described on Table 1.

Conclusion

AMR was high in GNB BSIs in the DR. High rates of ESBL render common cephalosporins sub-optimal for empiric treatment. PTZ retains in vitro susceptibilities despite cefepime resistance but clinical efficacy is controversial. CTX-M ESBLs may cause these resistance pattern in vitro. Further studies are needed to determine genetic mechanisms of resistance. Establishing antimicrobial stewardship programs with rapid diagnostic testing that identify mechanisms of resistance may promote judicious use of carbapenems and reduce further the risk of further development of AMR.

Disclosures

All authors: No reported disclosures.
507. Epidemiology of Community-Associated Carbapenemase + Producing Carbapenem-Resistant Enterobacteriacae Identified from the Emerging Infections Program, 2012–2017
Authors: See Isaac , Ansari Uzma , Reses Hannah , Grass Julian E , Epson Erin , Nadle Joelle , Bamberg Wendy M , Janelle Sarah J , Bower Chris W , Jacob Jesse T , Vaeth Elisabeth , Wilson Lucy E , Lynfield Ruth , VonBank Brittany , Snippes Vagnone Paula , Hancock Emily B , Phipps Erin C , Dumyati Ghinwa , Tsay Rebecca , Cassidy Maureen , Kainer Marion A , Mounsey Jacquelyn , Muleta Daniel , Bulens Sandra N , Karlsson Maria , Duffy Nadezhda , Lutgring Joseph
Published: October 2019

Background

Carbapenemase-producing (CP-) carbapenem-resistant Enterobacteriaceae (CRE) have been almost exclusively linked to extensive healthcare exposure and are of significant concern due to limited treatment options and potential for plasmid-mediated spread of resistance. We report on CP-CRE in community-dwelling individuals.

Methods

We used 2012–2017 active, laboratory and population-based surveillance data for CRE from CDC’s Emerging Infections Program sites (9 sites by 2017). Cases were the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. from a normally sterile body specimen or urine in a surveillance site resident meeting a CRE phenotype (figure) in a 30 day period. Epidemiologic data were obtained from chart review. Cases were community-associated (CA) if not isolated after the first three days of a hospital stay; without inpatient healthcare, dialysis, or surgery in the year prior; and without indwelling medical devices within two days prior to culture. A convenience sample of isolates was tested at CDC by real-time PCR to detect blaKPC, blaNDM, blaOXA-48-like, blaVIM, or blaIMP.

Results

Of 4023 CRE cases, 699 (17%) were CA, from which 297 isolates were tested; 20 (7%) were CP-CRE, from 18 patients (2 had repeat isolation of the same gene/species). The median age was 68 years (range: 33–91), and 14 (78%) were female. Patients were from 7 sites (range: 1–4/site). Their CP-CRE (10 blaKPC, 6 blaNDM, and 2 blaOXA-48-like) were from three species (10 K. pneumoniae, 6 E. coli, 2 E. cloacae) and isolated from urine (n = 16) and blood (n = 2). Among those with CP-CRE from urine, 12 (75%) had clinical diagnoses of urinary tract infections and the rest had no infection documented. Overall, 7 (39%) were admitted to a hospital within 30 days of culture; none died during hospitalization. Most (n = 13; 72%) had underlying medical comorbidities, most commonly urinary tract abnormalities (n = 5; 28%) and diabetes mellitus (n = 5; 28%). Three (17%) had international travel within two months prior to culture.

Conclusion

CA CP-CRE were found in most surveillance sites but are rare, occurring primarily in older patients with underlying medical conditions. Patient interviews are planned to determine whether CA CP-CRE may be associated with distant or undocumented healthcare exposures.

Disclosures

All authors: No reported disclosures.
515. Acquisition of Antibiotic-Resistant Gram-Negative Bacteria in the Benefits of Universal Glove and Gown (BUGG) Cluster Randomized Trial
Authors: Harris Anthony , Morgan Daniel , Harris Lisa , Magder Laurence S , O’Hara Lyndsay M , Johnson Kristie
Published: October 2019

Background

The Benefits of Universal Gloves and Gowns (BUGG) randomized trial found a decrease in MRSA acquisition, no effect on VRE acquisition and no increase in adverse events with the intervention of wearing gloves and gowns for all patient contact in the intensive care unit (ICU). The objective of the study was to assess whether wearing gloves and gowns for all patient contact in the ICU decreases the acquisition of antibiotic-resistant Gram-negative bacteria.

Methods

Design: Secondary study of the BUGG cluster-randomized trial.

Participants: 20 medical and surgical ICUs in 20 US hospitals.

Intervention: Healthcare workers were required to wear gloves and gowns when entering any patient room compared with standard care. Main outcomes and measures: The primary composite outcome was acquisition of any antibiotic-resistant Gram-negative bacteria based on surveillance cultures collected on admission and discharge. Secondary outcomes were acquisition of carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacteriaceae, or ESBL-producing Enterobacteriaceae.

Results

For the primary outcome, the intervention had a RR of 0.90 (95% CI 0.71 to 1.12, P = 0.34). Effects on the secondary outcomes were: carbapenem-resistant Enterobacteriaceae [RR 0.86 (95% CI, 0.60 to 1.24), P = 0.43], carbapenem-resistant Acinetobacter [RR 0.81 (95% CI, 0.52 to 1.27) P = 0.36], carbapenem-resistant Pseudomonas [RR 0.88 (95% CI, 0.55 to 1.42) P = 0.62], ESBL producing bacteria [RR 0.94, (95% CI, 0.71 to 1.24) P = 0.67].

Conclusion

The association of universal glove and gown use in the ICU with acquisition of antibiotic-resistant Gram-negative bacteria was inconclusive. The observed rate ratios for all five outcomes suggest that the intervention was protective, however, none were statistically significant. The study was likely underpowered to detect statistical significance for the effect sizes found. Individual hospitals should consider implementing the intervention based on the importance of these organisms at their hospital, effect sizes, confidence intervals, and cost.

Disclosures

All authors: No reported disclosures.
517. Treatment Patterns of Hospitalized Adults with Infections Due to Carbapenem Non-Susceptible Gram-Negative Organisms in a Large Electronic Health Record Database in the United States
Authors: Burton Tanya , Anderson Amy , Seare Jerry , Dillon Ryan J , McCann Eilish
Published: October 2019

Background

Infections caused by carbapenem non-susceptible (C-NS) Gram-negative (GN) organisms pose a major threat, due in part to limited treatment options. The aim of this study was to assess treatment patterns for these infections in a large US electronic health record database.

Methods

A retrospective cohort study of hospitalized adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), bacterial pneumonia (BP), or bacteremia (BAC) due to C-NS (resistant/intermediate susceptibility to carbapenem) GN organisms from January 2013 to March 2018. Patients with inherently C-NS organisms (e.g., Pseudomonas aeruginosa to ertapenem) were only included if resistance to another carbapenem was identified. The index date was the date of first C-NS culture in a qualifying hospitalization (±3 days from admission/discharge). Clinical characteristics and administered treatments were assessed from admission to discharge with variables summarized descriptively and stratified by infection type.

Results

7,702 patients met inclusion criteria: 31% cUTI ± BAC, 24% BP ± BAC, 21% cUTI + BP ± BAC, 17% cIAI ± BAC, cUTI, or BP, 7% BAC only. The median age was 66 years, ranging from 60 (BAC) to 69 (cUTI) years; male, 57%. The most common pathogens were Pseudomonas aeruginosa (64%) and Klebsiella pneumoniae (15%). Antibiotics were administered to the majority of patients (87%); of which, 79% received combination therapy (median classes: 3, maximum: 7), the remainder received monotherapy. For antibiotic-treated patients, 93% initiated an antibiotic before the non-susceptibility status of the underlying organism was known. The most common classes given during the index hospitalization were: penicillin (49%), fluoroquinolone (44%), carbapenem (40%), cephalosporin (39%), aminoglycoside (28%) (by infection type, Figure 1). Eleven percent of patients received colistin/polymyxin B.

Conclusion

Varied antibiotic use was observed in this cohort, with carbapenems frequently detected despite the C-NS nature of the underlying GN organisms. The use of antibiotics to which organisms are non-susceptible could lead to poor health outcomes, supporting the need for new targeted therapies to treat C-NS infections.

Disclosures

All authors: No reported disclosures.
523. Dual vs. Triple Antibiotic Therapy for Carbapenem-Resistant Acinetobacter baumannii Infections
Authors: Markelwith Justin Patrick , Vyas Nikunj M , Condoluci Mark , Kim Sungwook
Published: October 2019

Background

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain some of the most difficult to treat due to extremely high rates of resistance. The purpose of this study was to compare the efficacy of dual vs. triple targeted antibiotic regimens for CRAB infections.

Methods

This was an IRB approved retrospective cohort study performed at a 607-bed community health system between January 2016 and December 2018. Patients were included in the analysis if they were ≥18 years old and received antibiotics for CRAB for ≥72 hours. Patients were excluded if they were pregnant and had CRAB isolated solely from the urine. The primary endpoints of the study were differences in all-cause in-hospital mortality (ACIM) and clinical cure (CC) rates for patients treated with dual vs. triple antibiotic therapy. The secondary endpoint result focused on the difference in length of stay (LOS) between treatment groups. A sub-group analysis was performed for patients treated with tigecycline vs. minocycline combination therapy to determine differences ACIM and CC, and LOS. A multi-logistic regression analysis (MLRA) was performed to determine patient factors that were associated with ACIM and CC.

Results

A total of 32 patients were included in the primary analysis. No difference was seen in ACIM between dual vs. triple antibiotic groups (9.5% vs. 18.2%, P = 0.59). CC (63.6% vs. 57.1%, P = 1.0) and LOS (12 vs. 11 days, P = 1.0) was similar amongst patients treated with dual vs. triple antibiotic group. No differences were seen in ACIM (15.4% vs. 16.7% P = 1.0), CC (83.3% vs. 69.2%, P = 1.0) and LOS (15 vs. 14 days, P = 1.0) between tigecycline and minocycline combination therapy groups. The MLRA revealed a positive association with increased serum creatinine and ACIM (OR 3.29, 95% CI 1.35–8.04; P = 0.009) as well as shorter time to appropriate antibiotic therapy and clinical cure (OR 1.49, 95% CI 1.02–2.20; P = 0.04). CRAB isolates were more likely to be susceptible to minocycline vs. tigecycline (83% vs. 18%, P = 0.003).

Conclusion

No differences were seen in ACIM, CC and LOS between dual vs. triple antibiotic groups. Minocycline tends to sustain better susceptibility toward CRAB vs. tigecycline. Elevated serum creatinine was found to be a predictor for ACIM while shorter time to appropriate antibiotic therapy was associated with CC.

Disclosures

All authors: No reported disclosures.
536. Challenges in Using MALDI-TOF Technology to Assess for KPC Resistance in Klebsiella pneumoniae isolates in America
Authors: Thompson Michael Christopher , Banach David , Nishimura Christina , Muyombwe Anthony
Published: October 2019

Background

The emergence of Klebsiella pneumoniae Carbapenemase-producing Enterobacteriaceae (KPC-E) has created a major public health concern. In clinical practice, rapid identification of KPC-KP has important implications for clinical management and infection control. In some settings matrix-assisted laser desorption ionization time of flight (MALDI-TOF) software has been used for rapid detection of KPC producing K. pneumoniae with high sensitivity and specificity. Genomic sequencing has determined that the 11.09 m/z peak is related to protein expression from the P109 gene found mostly in Tna4401a isoform among KPC-E. In our study, we evaluated the use of MALDI-TOF automated detection software to evaluate for KPC detection among a diverse group of KPC-E isolates.

Methods

We tested 52 KPC-E isolates from various hospitals in Connecticut and the Centers for Disease Control and Prevention (CDC) Antibiotic Resistance (AR) Bank. All specimens were verified as KPC-producing strains by detection of the blaKPCgene through polymerase chain reaction. Protein extraction using the standard extraction method was performed on sub-cultured isolates. Each isolate was tested three times on MALDI-TOF MS with the incorporated bio-subtype KPC module. An organism confidence or log score value of 2 or higher was considered valid.

Results

Among 52 tested KPC-K. pneumoniae isolates, 44 (85%) were from various hospitals in Connecticut, eight (15%) came from the AR Bank. Only 15 (25.1%) of the isolates were detected as KPC-producing using the MALDI-TOF KPC module. Further investigation by peak analysis confirmed all 15 isolates detected positive demonstrated a peak at 11.09 m/z. The 11.09 m/z peak was not found in the 37 specimens that were not detected.

Conclusion

The results from our study suggest low sensitivity using this software and contradicts results seen in previous European studies. The Tna4401a isoform is often seen in KPC-2 strains, which may be less prevalent in our sample of isolates, explaining the poor sensitivity of MALDI-TOF. Further study is needed to explore this finding and potential opportunities for MALDI-TOF for rapid identification of KPC-KP.

Disclosures

All authors: No reported disclosures.