bluuebunny/crossref_metadata_2025 huggingface dataset:
392. Epidemiology and Treatment Outcome of Gram-Negative Polymicrobial, Gram-Positive Polymicrobial and Mixed Polymicrobial Prosthetic Joint Infection
Authors: Hooshmand Babak , Youssef Dima , Riederer Kathleen M , Szpunar Susan M , Coyle Meredith M , Bhargava Ashish
Published: October 2019

Background

Polymicrobial prosthetic joint infections (PMPJIs) are rare but treatment is usually challenging. Published studies described the PMPJIs without differentiating the component pathogens. We assessed clinical features and treatment outcome among Gram-negative polymicrobial (GNPM), Gram-positive polymicrobial (GPPM) and mixed polymicrobial (MPM) PJIs.

Methods

A retrospective cohort was studied at three Ascension hospitals in Detroit from January 2012 to December 2018. Cases were identified using the International Classification of Diseases, 9th and 10th Revision code specific for PJIs. Patient’s electronic medical records were reviewed.

Results

38 patients with PMPJI with a mean age of 67 years. were identified. 71% patients were female and caucasians. Nineteen (50%) patients had MPM, 16 (42%) had GPPM and 3 had GNPM. Among MPM PJIs, 14 (74%) involved hips, 4 (21%) knee and 1 (5%) ankle joint. Among GPPM PJIs, 7 (44%) involved hips, 8 (50%) knee and 1 (6%) shoulder joints. Among GNPM PJIs, 1 (33%) involved hip and 2 (67%) involved knee joints. 4 (21%), 1 (6%), and 1 (33%) patients had diabetes among MPM, GPPM and GNPM, respectively. Symptom onset of less than a week was noted in 13 (68%), 5 (31%), 3(100%) and of more than 3 weeks in 3 (16%), 7 (43%) and in 0 among MPM, GPPM and GNPM, respectively. 18 (95%), 12 (75%) and 2 (67%) patients presented with pain; 16 (84%), 6 (38%) and 3 (100%) patients had drainage among MPM, GPPM and GNPM, respectively. Among MPM PJIs, 12 (63%) underwent debridement, antibiotics and implant retention (DAIR), 2 (11%) for two stage exchange, 4 (21%) for chronic suppressive therapy and 1 (5%) had an amputation. 6 (58%) were readmitted within 6 months; 3 (50%) required prosthesis removal, 1 (4%) each died, was made hospice and was lost to follow-up. Among GPPM PJIs, 12 (75%) underwent DAIR and 4 (25%) went for two stage exchange. 9 (69%) patients among GPPM PJIs were readmitted in 6 months and 3 (50%) required prosthesis removal. All 3 of GNPM PJIs underwent DAIR and none were readmitted in 6 months.

Conclusion

Pain and drainage were common presenting symptoms. All GNPM PJIs presented within 1 week of symptoms and were treated successfully with DAIR. MPM and GPPM PJIs had high readmission rates and 6/26 (23%) managed with DAIR required prosthesis removal.

Disclosures

All authors: No reported disclosures.
410. Influence of Pre-season Antibody Titers to Influenza on Influenza Risk in a Cohort of Healthcare Personnel
Authors: Rattigan Susan M , Gorse Geoffrey , Kirpich Alexander , Cummings Derek , Rodriguez-Barradas Maria C , Simberkoff Michael , Bessesen Mary T , Gibert Cynthia L , Nyquist Ann-Christine , Price Connie S , Reich Nicholas , Brown Alexandria , Radonovich Lewis , Perl Trish M , Perl Trish M
Published: October 2019

Background

Influenza (flu) and other respiratory viruses circulate regularly throughout healthcare systems, often placing healthcare personnel (HCP) at high risk for illness. Hemagglutination inhibition (HAI) titers are associated with protection from flu illness, though few studies have characterized HAI in HCP. The Respiratory Protection Effectiveness Clinical Trial (ResPECT), provided HAI titers and data to assess infection risk based on four flu seasons. Participants from multiple outpatient settings wore respiratory protection within six feet of symptomatic patients.

Methods

Serological samples obtained at the beginning and end of each season and anterior nasopharyngeal swabs were taken randomly and when participants reported respiratory symptoms were assessed. Our primary outcome was PCR-confirmed influenza.

Results

During 5,180 participant-seasons of observation, 128 PCR-confirmed influenza A infections (20 H1N1, 108 H3N2) and 34 PCR-confirmed influenza B infections. 4,041 (78%) reported receiving an annual influenza vaccine. Each log base 2 increase in titer subtype-specific titer reduced the hazard of influenza infection with A/H3N2 by 18%(Relative Risk (RR) 0.82 95% CI 0.72,0.94), by 28% for influenza B (RR 0.72 95% CI 0.56,0.92 and by 25% for influenza A H1N1 (RR 0.75 95% CI 0.57–1.0). After adjusting for HAI titers, age was not significantly associated with risk for any of the subtypes.

Conclusion

In this prospective cohort of monitored HCPs, these findings support the current literature demonstrating that HAI titers are associated with protection from influenza infection. The relationship between HAI titers, influenza, and vaccination is complex, however. Vaccination was not shown to be associated with infection outcome in our model, though their effect may be difficult to separate from their effect on HAI titers.

Disclosures

Trish M. Perl, MD, MSc, 7–11: Advisory Board; medimmune: Research Grant.
418. Testing and Positivity Rates for Gonorrhea and Chlamydia in a Large Federally Qualified Health Center System
Authors: Douglas Claudia M , O’ Leary Sonja C , Tomcho Margaret M , Wu Florence J , Federico Steven J , Frost Holly M
Published: October 2019

Background

Gonorrhea (GC) and Chlamydia (CT) are the most reported sexually transmitted infections in the United States. Little is known about testing and positivity rates for GC/CT in clinical practice, particularly for male patients. In this study, we analyzed rates of GC/CT testing and positivity among 11–24 years old patients presenting to a system of federally qualified health centers (FQHC).

Methods

This retrospective data review was conducted at Denver Health (DH) in Denver, CO. Data were abstracted for 11–24 years old who were seen at least once at a DH FQHC in 2018. Abstracted data included patient age, gender, clinic location, and testing for GC/CT. The percentage of patients tested ≥1 time within the preceding year and the percentage of tested patients that were positive for GC and/or CT ≥1 time were calculated along with Wald 95% confidence intervals.

Results

In total, 34,416 unique patients were included. GC/CT testing was completed for 7.3% (95% CI: 6.8%, 7.6%) of 11–15 years old, 30.6% (95% CI: 29.5%, 31.6%) of 16–18 years old, and 45.6% (95% CI: 44.8%, 46.4%) of 19–24 years old. Rates of testing varied by gender and age and were lowest among males and younger patients (Figure 1). Of patients tested, 11.4% (95% CI: 10.7%, 12.1%) of females and 9.1% (95% CI: 7.8%, 10.4%) of males were positive for CT and 1.7% (95% CI: 1.4%, 2.0%) of females and 2.3% (95% CI: 1.6%, 2.9%) of males were positive for GC (Figure 2). Though less likely to be tested than older patients, females 11–15 years old had the highest rates of GC (2.1%; 95% CI: 1.2%, 3.0%) and the second highest rate of CT (13.5%; 95% CI: 11.3%, 15.6%) among females tested.

Conclusion

Despite efforts to improve GC/CT screening, less than 50% of 11–24 years old patients were tested within the prior year. Rates of GC/CT were higher than previously reported, particularly for females less than 16 years old. Male patients were less likely to be tested; however, the males who were tested had higher GC positivity rates and only slightly lower rates of CT than females who were tested. Future studies evaluating the effectiveness of interventions to reduce GC/CT among 11–24 years old are critically needed.

Disclosures

All authors: No reported disclosures.
421. Return of Results in Sexually Transmitted Infection Research: The Ethics of Notification and Treatment
Authors: Grubbs Joshua C , Rietmeijer Cornelis , Millum Joseph , Kilmarx Peter H
Published: October 2019

Background

In prevalence studies of sexually transmitted infections (STI), investigators often provide syndromic management for symptomatic participants, but may provide no specific treatment for asymptomatic individuals with positive test results due to the delays between sample collection and processing. It is unknown how frequently positive test results are returned to participants so that they know to seek treatment. The potential outcome, untreated study participants with documented infection, is concerning given the history of ethical lapses in STI research and the vulnerability of many STI study populations.

Methods

To characterize the extent of this issue, 82 prevalence studies from the World Health Organization’s (WHO) Report on global sexually transmitted infection surveillance, 2018, were reviewed to determine whether return of test results were reported. Studies were classified as either results returned, unspecified, or other. Publications were coded by country income in accordance with World Bank designations based on the study population’s location(s).

Results

Nearly half (45%) of the cited studies did not specify if participants were notified of their STI test results. Most study populations (78%) were in lower- and middle-income countries (LMIC) while 20% were in high-income countries (HIC). The remaining 2% of studies screened populations in both LMIC and HIC. Return of results was similar across income groups. Half of papers (50%) in HIC clearly indicated the return of results, whereas 44% were unspecified and one publication (6%) indicated results were not returned due to an unlinked-anonymized testing protocol (other). Results were returned in 53% of studies conducted in LMIC and not specified in 47%.

Conclusion

A substantial proportion of STI prevalence studies cited in a 2018 WHO report did not specify if participants received their test results. Institutional approval and informed consent are critical, but insufficient for ethical research. Clinically relevant results should be returned to study participants and treating clinicians to ensure appropriate management of identified infections, if not treated during research. This is especially important in STI research in vulnerable populations.

Disclosures

All authors: No reported disclosures.
427. Putting the ‘Eye’ in Spirochetes
Authors: Khalil Sarwat , Fida Madiha , Challener Douglas W , Tan Eugene , Sohail Muhammad R , Abu Saleh Omar
Published: October 2019

Background

Ocular syphilis is an infrequent presentation of Treponema pallidum infection. It is often seen in association with neurosyphilis but can occur in isolation as well. Here we describe a case series of 10 patients with ocular syphilis seen at our institution.

Methods

Patients with a diagnosis of ocular syphilis at the three sites of Mayo Clinic were identified from June 2006 to February 2019. Patient’s baseline characteristics, clinical presentation, diagnostic testing, and treatment were abstracted from Electronic Medical Records.

Results

We identified 10 patients (17 eyes) during the study period, half being diagnosed in the last 5 years. The median age was 51 years (IQR 21–66), and the majority were males (7/10). Characteristics of the patients are outlined in Table 1. Common presenting symptoms included vision loss (8/10), photophobia (4/10), and irritation (5/10). Seven of 10 patients had bilateral involvement. Of the 17 eyes, 59% had pan-uveitis and 82% had disc edema (Table 2). Rapid Plasma Reagin (RPR) was positive in 9 patients and median serum RPR was 1:128 (IQR 1:2-1:1024). One patient was diagnosed with a positive TP-PA, and characteristic ocular findings. One patients had positive 16S Ribosomal RNA Gene PCR/Sanger Sequencing on vitreous humor specimen for Treponema species. The majority of patients had isolated ocular symptoms at presentation; two patients also had an associated skin rash. All patients underwent a lumbar puncture (LP). Half had pleocytosis (TNC > 5) and elevated protein elevated (mean 63.6 mg/dL), although not significantly high. 3/10 patients had VDRL positive in the CSF. Protein levels were much higher in those with positive VDRL. Each patient was treated with intravenous (IV) penicillin for at least 2 weeks. Nine patients received ocular steroids as well. At last available follow-up, 8 had complete and 1 had partial resolution. One had worsened eye findings with eventual scarring.

Conclusion

Our findings are congruent with increasing incidence of ocular syphilis nationwide. Bilateral eye involvement and pan-uveitis were the most common ocular findings. Although only 3 patients had a positive VDRL in the CSF, pleocytosis and elevated protein were found in a large number of patients. Majority of the patients had clinical resolution with appropriate treatment.

Disclosures

All authors: No reported disclosures.
432. Qualitative Differentiation of Genital Ulcer Disease Etiology via Nucleic Acid Amplification Testing (NAAT)
Authors: McGowin Chris L , McCune Stephen , Engstrom-Melnyk Julia
Published: October 2019

Background

Genital ulcers (GUs) remain a common reason that both men and women seek treatment at US sexual health clinics. Presumptive diagnosis based solely on the macroscopic lesion characteristics is insensitive for differentiating between the common etiologies of GUs, which include HSV1/2, VZV, and syphilis. Given the ongoing and rapidly-expanding Syphilis epidemic, more accurate and timely identification of GU etiology would facilitate accurate therapeutic decision making, promote antibiotic stewardship, and have positive impacts on public health. The current study describes diagnostic workflows that allow for sequential/reflex or parallel GU testing, relying on a combination of IVD and published NAAT-based solutions, performed on the cobas® 4800 and/or cobas® 6800 Systems, to detect HSV1/2, VZV, and T. pallidum from a single specimen.

Methods

Commercially available control material for HSV1, HSV2, VZV, and T. pallidum were spiked into MSwab™ and cobasâ PCR medium at varying concentrations. The spiked medium was either aliquoted directly to cobas® PCR Media Secondary Tubes (for testing on the cobasâ 6800 System) or MSwabs were dipped directly into the spiked specimen vials and transferred to their respective collection tubes (cobasâ 4800 System). GU testing on the cobas® 4800 System was sequential: performing the cobas® HSV1 and 2 Test first, followed by VZV and T. pallidum detection using residual DNA eluates and the User Defined Workflow (UDF) software. Testing on the cobas® 6800 System allowed for parallel processing and simultaneous detection of the 4 targets utilizing the cobas omni Utility Channel, which supports a complete, automated Lab Developed Test workflow.

Results

Qualitative detection of HSV1, HSV2, VZV and T. pallidum was demonstrated on both systems.

Conclusion

Novel solutions that aim to reduce empiric therapy, or shorten the interval to treatment success, are critical for both diagnostic and antibiotic stewardship. Through parallel or sequential testing algorithms, panel testing schematics on either the cobas® 4800 and 6800 Systems allow for more accurate discrimination between GU etiologies that may help address the re-emergence of Syphilis in the USA.

Disclosures

All authors: No reported disclosures.
445. A Case of Disseminated Microsporidia Manifesting as Skin Lesions in a Patient with Acute Lymphoblastic Leukemia
Authors: Kaul Christina M , Kim Angela
Published: October 2019

Background

We present a case of a 65-year-old male with a history of acute B-cell lymphoblastic leukemia (ALL) who presented with fevers and skin lesions. The patient achieved remission after induction chemotherapy. Nineteen months after diagnosis, while on maintenance therapy, the patient presented as noted above. He was instructed to hold maintenance therapy and sent to the hospital.

Methods

 

Results

On examination, the patient was febrile. He had papules present on the forehead, chest, arms, legs, and back. Physical examination was otherwise unremarkable. Labs were notable for a white blood cell count of 3600/uL (absolute neutrophil 3100/uL) and creatine kinase (CK) of 593 U/L. Blood and urine cultures, Histoplasma, Varicella, Toxoplasma, HIV, and an acute hepatitis panel were negative. CT of the chest, abdomen, and pelvis was unremarkable. He was empirically started on micafungin and valacyclovir. However, he continued to have fevers and myalgias. Wound culture was negative for fungus after four weeks of growth. Skin biopsy immunostains were consistent with an unknown protozoan. Specimens were sent to an outside facility and yielded a diagnosis of Anncaliia algerae. Antibiotics were changed to albendazole and voriconazole, with subsequent improvement in all symptoms.

Conclusion

Microsporidia most commonly infect immunocompromised hosts. Clinical manifestations of microsporidiosis are extremely diverse. Oftentimes, symptoms are not present in those found to be infected with Microsporidia. A disseminated disease has been identified but remains rare. Although Microsporidia have been identified as a cause of infection in immunocompromised patients, there are few reports of infection in those diagnosed with cancer, and only a few cases have been due to Anncaliia algerae. In studies pertaining to ALL patients, roughly one-fifth of patients were identified as being infected with Microsporidia, but most did not have symptoms. This is the first reported case of disseminated Microsporidia in a patient with ALL and the first disseminated infection presenting as a skin manifestation. Of identified cases of disseminated Microsporidial infection, mortality was high. Thus, prompt recognition of Microsporidia as a cause of infection in patients with ALL is of utmost importance.

Disclosures

All authors: No reported disclosures.
449. Epidemiology of Combat-Related Deep Soft-Tissue Wound Infections
Authors: Stewart Laveta , Li Ping , Blyth Dana M , Blyth Dana M , Petfield Joseph , Campbell Wesley R , Tribble David
Published: October 2019

Background

Deep soft-tissue infections (DSTIs) are a common complication of combat-related extremity trauma. We present an epidemiologic assessment of combat-related DSTIs among wounded military personnel.

Methods

Wounded personnel were included in the analysis if they sustained an open combat-related extremity wound (2009–2014), were admitted to a participating US military hospital, had a DSTI as the first confirmed extremity wound infection (within 30 days post-injury), started antibiotics ±3 days of DSTI diagnosis, and received ≥5 days of directed antibiotic treatment.

Results

Among 1961 combat casualties with open extremity wounds, 259 had a DSTI diagnosis with 173 (67%) having only 1 index DSTI and 86 (33%) having >1 index DSTI diagnosed on the same day. Nearly all patients (95%) were injured via a blast mechanism. Patients with >1 index DSTI were more severely injured (median injury severity score: 35 vs. 33; P = 0.009) and required large volume blood transfusions within 24 hours of injury (median units: 23 vs. 17; P < 0.001). Initial empiric antibiotic treatment largely involved carbapenem and vancomycin (77% and 72% of patients, respectively). For diagnosis timing, 130 (50%) patients had an early DSTI diagnosis (≤7 days post-injury), while the remaining 129 (50%) patients had a delayed diagnosis (>7 days post-injury). Patients with early DSTI diagnoses more often had >1 index DSTI (47% vs. 19% with delayed DSTI; P < 0.001). Polymicrobial DSTIs were common (73% of early DSTIs; 58% of delayed DSTIs) with Enterococcus spp. most frequently identified (56% of early DSTIs; 31% of delayed DSTIs) as well as Enterobacter spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. Moreover, 26% and 39% of early and delayed DSTIs had multidrug-resistant Gram-negative bacteria. Receipt of >20 units of blood within 24 hours of injury and having >1 index DSTI were independently associated with an early DSTI diagnosis (odds ratio [OR]: 3.21; 95% CI: 1.47–7.02 and OR: 2.98; 95% CI: 1.63–5.42, respectively).

Conclusion

Multiple index DSTIs and massive blood transfusion requirement are associated with early infection onset post-injury. Awareness of wound microbiology findings relative to DSTI onset provides guidance on empiric antimicrobial therapy.

Disclosures

All authors: No reported disclosures.
458. Diagnostic Accuracy and Management of Suspected Moderate to Severe Cellulitis Referred to an Infectious Diseases Outpatient Parenteral Antibiotic Clinic: A Prospective Cross-Sectional Study
Authors: Piszczek Jolanta , Partlow Eric , Daniels Shay-Anne , Semproni Milena , Ghesquiere Wayne
Published: October 2019

Background

Moderate to severe cellulitis is a common reason for presentation to the emergency department and administration of intravenous antibiotics. Misdiagnosis of cellulitis occurs frequently as the disease can masquerade as a wide variety of noninfectious and infectious problems. There are currently no studies evaluating the impact of infectious diseases physicians on the diagnostic accuracy and management of cellulitis referred to an outpatient parenteral antibiotic clinic from the emergency department. The objective of this study was to quantify the prevalence of misdiagnosed moderate to severe cellulitis through an evaluation by an infectious diseases specialist, characterize the alternative diagnoses, and assess variables associated with misdiagnosis.

Methods

A prospective cross-sectional study of adults referred from emergency departments with presumed moderate to severe cellulitis to an outpatient parenteral antibiotic clinic staffed by infectious diseases specialists.

Results

301 consecutive patients with presumed cellulitis were evaluated over a 6-month period. A concurring diagnosis of cellulitis was found in 170 patients (56.5%), for a misdiagnosis rate of 43.5% (131/301). Table 1 summarizes the alternative diagnoses. Infectious conditions other than cellulitis were the most common (63/301; 20.9%), with abscess being present in 23 (7.6%) of patients. Fifty-two of 301 (17.3%) of the diagnoses were noninfectious and 16/301 (5.3%) patients had a dual diagnosis where minor cellulitis was present, but secondary to another, predomintating condition. The presence of stasis dermatitis (OR 6.62, P = 0.013) and a history of physical trauma (OR 1.76, P = 0.046) were associated with a misdiagnosis. 31.9% (107/335) of antibiotic regimens prescribed by emergency physicians were inappropriate or sub-optimal compared with 7.9% (22/280) of those ordered by infectious disease doctors.

Conclusion

Moderate to severe cellulitis was incorrectly diagnosed in nearly half of the patients referred for intravenous antibiotics and resulted in a high rate of unstewardly antimicrobial use. Infectious diseases physicians at an outpatient antibiotic clinic improved the diagnostic accuracy and management of this complicated condition.

Disclosures

All authors: No reported disclosures.
464. Fecal Staphylococcus aureus in the Neonatal Intensive Care Unit
Authors: Carl Mike , Milburn Olivia , Uible Emma , Haslam David
Published: October 2019

Background

Staphylococcus aureus colonization in infants in the neonatal intensive care unit (NICU) often leads to repeated infections and severe disease. Methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) infections are major causes of NICU outbreaks. Current national practice in NICUs utilizes nare swab surveillance for S. aureus. We hypothesize that infants colonized in the stool with S. aureus may go unrecognized particularly when nare swab negative, allowing for a transmission reservoir. While it is unclear why some S. aureus nare carriers are also stool colonized, isolates tend to have clonality. A true prevalence of S. aureus fecal carriage is not well understood and variable.

Methods

Available stool samples were prospectively collected from 42 of 55 infants admitted in a level IV NICU on a single day, per Cincinnati Children’s institutional review board approval. Nare swab results were obtained from electronic medical records. DNA was isolated from stool and shotgun metagenomic sequencing was performed via Hiseq Illuminex 2500. The presence of S. aureus and MRSA were defined as having >100 sequencing reads and a mecA DNA read fraction ratio >40 per stool sample, respectively.

Results

Of the 42 stool samples sequenced, 33 were S. aureus (15 MSSA, 18 MRSA) positive. All infants with nare positive MSSA (n = 9) were colonized in the stool with a 93% and 100% sensitivity and specificity, respectively. While infants with nare positive MRSA (n = 10) were stool colonized with 100% and 83% sensitivity and specificity, respectively. Three nare positive infants with MRSA had S.a. in the stool but lacked the presence of mecA. When comparing clinical nare swabs to stool metagenomic surveillance, sensitivities were 60% for MSSA and 56% for MRSA.

Conclusion

Infant colonization of S. aureus in the NICU remains a major problem despite current national surveillance and isolation practices. We found that nare swab surveillance for S. aureus in infants significantly underestimated colonization rates when compared with shotgun metagenomics of stool. These results suggest that nare swabs alone may not have adequate sensitivity and the implementation of stool surveillance should be considered to augment current practices. Future study is necessary to understand how the S. aureus stool reservoir contributes to transmission

Disclosures

All authors: No reported disclosures.
470. Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in Patients with Significant Drug Abuse: Outcomes from Global Phase 3 Studies of Delafloxacin (DLX)
Authors: Overcash J Scott , O’Riordan William , Quintas Megan , Lawrence Laura , Tseng Carol , Cammarata Sue
Published: October 2019

Background

Delafloxacin (DLX), an IV/oral anionic fluoroquinolone antibiotic, is approved for the treatment of ABSSSI including those due to MRSA and Gram-negative pathogens including P. aeruginosa. Two global phase 3 ABSSSI trials included patients with substance abuse including IV drugs.

Methods

Two multicenter, double-blind, double-dummy trials of adults with ABSSSI randomized patients 1:1 to receive either DLX monotherapy or vancomycin 15 mg/kg + aztreonam (VANAZ) for 5–14 days. Study 302 used DLX 300 mg BID IV only; study 303 used DLX 300 mg BID IV for 3 days with a mandatory blinded switch to DLX 450 mg oral BID. Key endpoints were Objective Response at 48–72 hours with ≥20% reduction in lesion size, and Investigator assessment of outcome at Follow-up (FU, Day 14), both in the Intent To Treat population.

Results

In the 2 studies, 620 patients with substance abuse, excluding alcoholism, including heroin, cocaine and methamphetamine abuse, were randomized in the United States. 71% were male with mean age 44 years. Average erythema area at baseline was ~230 cm2. 16% percent had cellulitis, 30% abscesses, and 53% wound. S. aureus (SA) was the most frequent pathogen. DLX was non-inferior to VANAZ for the Objective Response: 85.9% DLX vs. 84.4% VANAZ [∆2.6 (95% CI −2.9, 8.1)] as well as the assessment of outcome at FU: 82.0% DLX vs. 79.3% VANAZ [∆3.2 95% (CI −3, 9.4)]. Micro success in evaluable patients with SA was seen in 99.1% DLX vs. 100% VANAZ as well as 98.2% DLX vs. 100% VANAZ in patients with MRSA. The overall % of patients with at least one adverse event (AE) was comparable for DLX (49.0%) compared with VANAZ (56.1%). The most frequent treatment-related AEs were gastrointestinal in nature, including nausea seen in 9.7% DLX and 5.8% VANAZ patients, primarily mild to moderate in severity. There were no cases of C.difficile diarrhea. Discontinuations due to treatment-related AEs were lower with DLX (0.3%) compared with VANAZ (2.2%).

Conclusion

Fixed-dose monotherapyDLX was comparable to VANAZ in treatment of ABSSSI in patients with substance abuse based on the Objective Response as well as investigator-assessed outcome. DLX was also comparable to VANAZ in treating patients with SA and MRSA. DLX appears effective and well tolerated in patients with ABSSSI and significant substance abuse.

Disclosures

All authors: No reported disclosures.
475. High Rate of Extended-Spectrum β-Lactamase Producing Gram-Negative Infections and Associated Mortality in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Tufa Tafese B , Beyene Tufa Takele , André Fuchs , Torsten Feldt
Published: October 2019

Background

Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria have become a serious threat to global health. The rapid increase of ESBL-producing bacteria is associated with high mortality due to ineffective antibiotic treatment. To date, regular surveillance of multidrug-resistant (MDR) pathogens is lacking in Ethiopia. For this report, published data regarding ESBL-producing bacteria in different regions of Ethiopia were reviewed systematically. To our knowledge, this is the first systematic review from Ethiopia on ESBL-producing infections and associated mortality in the country.

Methods

A literature search was conducted in PubMed, PubMed Central, and Google Scholar from January 1, 1990 to April 28, 2019, using the following search terms: “ESBL producing Enterobacteriaceae,” “Gram-negative bacteria infection associated mortality,” and “Ethiopia.” Patient mortality associated with infections by ESBL-producing Gram-negative bacteria was recorded.

Results

Fourteen publications qualified for review. Totally, 1,782 Gram-negative bacteria isolated from 5,191 clinical samples were included. The phenotypic pooled rate of ESBL-producing Gram-negatives was estimated to be 52.9(95% CI: 50.5%–55.4%). Among different species, ESBL rates were 65. 7% (262/399) Klebsiella spp., 60.6% (20/33) for Enterobacter spp., 47.8% (22/46) for Citrobacter spp., 47.0% (383/815) for E. coli, 45.7% (85/186) for Salmonella spp., 27.8%(15/54) for Proteus spp., 16.7%(4/24) for P. aeruginosa, 14.3% (3/21) for Acinetobacter spps., and 40.5% (15/37) for others, respectively. ESBL genes were confirmed in three studies. blaCTX-M-1 and blaTEM were the predominately detected genes. Two studies reported mortality associated with Gram-negative infections and 86% (12/14) of the patients infected with ESBL-producing bacteria died.

Conclusion

In this meta-analysis, the pooled phenotypic prevalence of ESBL-producing pathogens is considerably high. Also, the mortality due to ESBL-producers is high but data are scarce. This highlights the need for establishing and upgrading of clinical microbiology laboratories in the country for routine antibiotic susceptibility testing. The capacity to detect ESBL genes is desirable for continuous surveillance of MDR.

Disclosures

All authors: No reported disclosures.
476. Risk Factors of Community-Onset Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Bacteremia in South Korea Using National Health Insurance Claims Data
Authors: Lee Yongseop , Soo Park Yoon , Kim Dokyun , Ah Kim Young , Hee Shin Jong , Uh Young , Seob Shin Kyeong , Hwan Shin Jeong , Hoon Jeong Seok
Published: October 2019

Background

Antibiotic resistance is a significant threat to public health not only in healthcare setting but also in community because antimicrobial-resistant infections can be transmitted in community. Although it is essential to know whether there are particular reasons that caused antibiotic-resistant infection in community, there is lack of evidence regarding risk factors for community-onset extended-spectrum β-lactamase-producing Klebsiella pneumoniae bloodstream infection (ESBL-KP BSI) in South Korea. In the present study, we aimed to reveal risk factors for community-onset ESBL-KP BSI.

Methods

From May 2016 to April 2017, patients with community-onset KP BSI (n = 408) from six sentinel hospitals in South Korea were included. The hospitals are located in different districts throughout South Korea, and had a total of 5,194 beds, ranged from 715 to 1,050 beds per hospital. Admission history and previous usage of antibiotics and medical devices before bacteremia were acquired from National Health Insurance claims data. Risk factors of ESBL-KP BSI were analyzed with a multivariable logistic regression model. PCR and sequencing for the identification of genes encoding ESBLs, and multilocus sequence typing were performed.

Results

Of 408 patient of community-onset KP BSI, 70 (17%) were ESBL-KP BSI patients. ESBL-KP isolates most frequently carried CTX-M-1-group ESBLs (74%, n = 52), followed by CTX-M-9-group ESBLs (16%, n = 11). Most prevalent sequence type (ST) among ESBL-KP isolates was ST48 (14%, n = 10). Among non-ESBL-KP isolates, ST23 was most prevalent (21%, n = 70). Analyzing with multivariate analysis, recent admission to long-term care hospital within 3 months (OR, 5.7; 95% CI, 2.1–15.6; P = 0.001), previous usage of trimethoprim-sulfamethoxazole (OR, 11.5; 95% CI, 2.7–48.6; P = 0.001), expanded-spectrum cephalosporin (OR, 2.2; 95% CI, 1.2–3.9; P = 0.01), and previous use of urinary catheter (OR, 2.3; 95% CI, 1.1–4.5; P = 0.02) were identified as independent risk factors for community-onset ESBL-KP BSI.

Conclusion

Recent admission to long-term care hospital, use of urinary catheter, recent usage of antibiotics were identified as risk factors for community-onset ESBL-KP BSI. Strict antibiotic stewardship and infection control measures in long-term care hospital are needed.

Disclosures

All authors: No reported disclosures.
485. Clinical and Molecular Epidemiology of Carbapenem Non-susceptible Citrobacter sp.
Authors: Babiker Ahmed , Evans Daniel R , Griffifth Marrisa P , Mettus Roberta T , McElheny Christi L , Clarke Lloyd , Harrison Lee , Doi Yohei , Shields Ryan K , Van Tyne Daria
Published: October 2019

Background

Carbapenem non-susceptible Citrobacter sp. (CNSC) are becoming increasingly recognized as healthcare-associated (HA) pathogens, but data on clinical and molecular epidemiology, species diversity and mechanisms of carbapenem resistance are lacking.

Methods

We reviewed patients at University of Pittsburgh Medical Center with CNSC positive cultures from 2000 to 2018. The diversity of CNSC species among a subset of isolates from all UPMC sites was confirmed by 16S rRNA typing, and the presence of carbapenemase enzymes in the same isolates was determined by PCR amplificon. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Significance of epidemiological trends over time was determined by linear regression, and correlation with antibiotic consumption was determined by cross-correlation using STATA v15.

Results

Between 2000 and 2018, 3% (78/2817) of all Citrobacter sp. were CNS. CNSC rates increased from 4% in 2000 to 10% in 2018 (R2 = 0.206, P = 0.05), as did carbapenem consumption (6.5–34.5 DDDs/1000, R2 = 0.831, P < 0.001) (Figure 1). Twenty-one isolates from 19 patients were available for additional analysis. Patients had multiple comorbidities (84%), frequently acquired CNSC in the healthcare setting (84%), were colonized with other organisms (68%), and had high rates of in-hospital mortality/discharge to hospice (47%) (Table 1). C. freundii was the dominant species identified (16/21), followed by C. farmeri (2/21), C. koseri (2/21), and C. werkmanii (1/21). Carbapenemases were identified in 14 isolates, including KPC (n = 12), NDM (n = 2), and OXA-48 (n = 1) (Table 2). Isolates were frequently susceptible to ceftazidime–avibactam (MIC median [IQR]: 2[0.5,8]) 81%) and meropenem-vaborbactam (86%) (MIC median [IQR] 0.12[0.3,0.5]) (Table 2).

Conclusion

CNSC species are diverse, have emerged as an HA pathogen at our center, and cause high rates of mortality. Further studies, including ongoing genome sequencing and analysis, are required to better elucidate CNSC diversity and resistance mechanisms.

Disclosures

All authors: No reported disclosures.
494. Fitness Cost of mcr-1-Mediated Colistin Resistance in Carbapenemase-Producing Klebsiella pneumoniae
Authors: Lin Yi-Tsung , Cheng Yi-Hsiang , Chou Sheng-Hua , Huang Ying-Chi , Chen Liang
Published: October 2019

Background

The emergence of mobile colistin resistance gene mcr-1, a plasmid-borne polymyxin resistance mechanism, in carbapenem-resistant Klebsiella pneumoniae is an alarming concern. However, previous studies showed that the acquisition of mcr-1 was associated with a significant biological fitness cost in K. pneumoniae. We aimed to study the impact of mcr-1 on the biological fitness in clinical carbapenemase-producing K. pneumoniae strains.

Methods

Clinical carbapenemase-producing K. pneumoniae strains were collected consecutively at the Taipei Veterans General Hospital between November 2017 and December 2018. The strain positive for mcr-1 was subjected to whole-genome sequencing to delineate its genomic features. Escherichia coli J53 strain was used as the recipient strain in plasmid conjugation assay and the transconjugants were selected with sodium azide and colistin. Plasmid stability was tested by serial passaging in antibiotic-free LB broth for 28 days. The growth rate was compared between the parental mcr-1-bearing strain and the plasmid-cured strain.

Results

One ST11 strain isolated from a fatal case with bacteremia (KP2509) was found to harbor blaKPC-2, blaOXA-48, and mcr-1. This strain was resistant to colistin (MIC=8 mg/L) and imipenem (MIC≥16 mg/L). Whole-genome sequencing of KP2509 showed that mcr-1, blaKPC-2 and blaOXA-48 were located on an IncHI-FIB type plasmid of 319 Kb, an IncFII type plasmid of 96 Kb, and an IncL type plasmid of 64 Kb, respectively. Conjugation efficiency of mcr-1-bearing plasmid was 2.24 × 10–4, and the colistin MIC of E. coli J53 transconjugant increased from 0.5 to 8 mg/L. The mcr-1-bearing plasmid in KP2509 showed high plasmid stability, and only ~1% were lost after 27-day passages. The resulting plasmid-cured strain (PC-KP2509) was susceptible to colistin (MIC=0.5 mg/L) and had a similar growth rate to that of parental mcr-1-bearing strain KP2509.

Conclusion

We identified an ST11 K. pneumoniae strain carrying blaKPC-2, blaOXA-48, and mcr-1 genes causing a fatal bacteremia. The large mcr-1-bearing plasmid confers a moderate level of colistin resistance but without significant biological fitness cost in carbapenemase-producing K. pneumoniae, which could result in a serious threat clinically.

Disclosures

All authors: No reported disclosures.
495. Risk Factors of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections Among Intensive Care Unit (ICU) Patients in a Tertiary Hospital in the Philippines
Authors: Torio Roderick Oreal , Paras Danielle Nicole T , Abad Cybele Lara R
Published: October 2019

Background

The threat of Carbapenem-Resistant Enterobacteriaceae (CRE) is increasing worldwide, and the epidemiology, risk factors, and outcomes of CRE in the Philippines is unknown.

Methods

We performed a retrospective case–control study of 128 CRE cases and Carbapenem-Susceptible Enterobacteriaceae (CSE) controls matched 1:1 based on site of infection and date of admission among all adult patients in the Intensive Care Unit (ICU) between January 2014 and May 2018 at The Medical City. Predictors of CRE infection among matched cases and controls were determined through multiple conditional logistic regression analysis. In-hospital mortality was analyzed using z-test of two proportions and length of stay among patients with CRE and CSE were compared.

Results

The mean age in both groups was similar at 65.8 (range 23–92) and 64.3 (range 23–98) years, respectively. There were more males among cases than controls [(76/128, 59%) vs. 62/128 (48%)]. Those with CRE were more likely to have a co-morbid illness and an invasive device. Pneumonia was the most common site of CRE infection (40%) followed by the urinary tract (27%). Enterobacter cloacae (54.68%) was the most common organism, followed by Klebsiella pneumoniae (30.46%). On univariate analysis, the use of piperacillin–tazobactam, third or fourth-generation cephalosporins and carbapenems, mechanical ventilation, and acute kidney injury (AKI) increased the risk of developing CRE infections by an OR of 7.5 (CI 1.88–29.95, P = 0.004), 9.32 (CI 1.48–58.59, P = 0.017), and 10.76 (CI 1.69–68.53, P = 0.012), respectively. Those with CRE had a higher in-hospital mortality than the CSE group [(49/79, 38.3%) vs. (33/95, 25.8%); P = 0.032]. Length of hospital stay among CRE cases was also longer with a mean of 43.9 vs. 28 days compared with controls.

Conclusion

In our cohort, older patients w/ comorbidities developed CRE with pneumonia being the most common site of infection. Prior use of broad-spectrum antimicrobials, mechanical ventilation and AKI appeared to increase the risk of CRE infection in the ICU. CRE infection also increased patient mortality and length of hospital stay. Interventions that target these risk factors should be undertaken to help prevent CRE infection.

Disclosures

All authors: No reported disclosures.
512. Healthcare-Acquired (HA) Carbapenemase-Producing Enterobacteriales (CPE) in Southern Ontario, Canada: To Whom Are We Transmitting CPE?
Authors: Jamal Alainna , Coleman Brenda , Johnstone Jennie , Katz Kevin , Muller Matthew P , Patel Samir , Melano Roberto , Rebbapragada Anu , Richardson David , Sarabia Alicia , Mubareka Samira , Poutanen Susan , Zhong Zoe , Kohler Philipp , McGeer Allison
Published: October 2019

Background

Though CPE in Canada are mainly acquired abroad, outbreaks/transmission in Canadian hospitals have been reported. We determined the incidence of HA CPE in southern Ontario, Canada, to inform prevention and control programs.

Methods

Toronto Invasive Bacterial Diseases Network (TIBDN) has performed population-based surveillance for CPE in the Toronto area/Peel region of southern Ontario, Canada, since CPE were first identified in October 2007. Clinical microbiology laboratories report all CPE isolates to TIBDN; annual lab audits are performed. Incidence calculations used first isolates as numerator; denominator (patient-days/fiscal year for Toronto/Peel hospitals) was from the Ontario Ministry of Health and Long-Term Care.

Results

The incidence of HA CPE has risen from 0 in 2007/2008 to 0.45 and 0.28 per 100,000 patient-days for all and clinical cases, respectively, in 2017/2018 (Figure, P < 0.0001). 190/790 (24%) incident cases of CPE colonization/infection in southern Ontario from October 2007 to December 2018 were likely HA (hospitalized in Ontario with no history of hospitalization abroad/high-risk travel). Eighty (25%) were female and the median age was 73 years (IQR 57–83 years). 157 (83%) had no prior travel abroad and 33 (17%) had prior low-risk travel. 122 (64%) had their CPE identified >72 hours post-admission (of which 83 also had ≥1 other prior Ontario hospitalization); 68 (36%) had their CPE identified at admission but had recent prior Ontario hospitalization. HA cases vs. foreign acquisitions were significantly more likely K. pneumoniae (48% vs. 38%, P = 0.02) and Enterobacter spp. (20% vs. 7%, P < 0.0001) and less likely E. coli (20% vs. 48%, P < 0.0001). Genes of HA vs. foreign acquisitions were significantly more likely blaKPC (34% vs. 12%, P < 0.0001) and blaVIM (12% vs. 2%, P < 0.0001) and less likely blaNDM±OXA (38% vs. 56%, P < 0.0001) and blaOXA (13% vs. 27%, P = 0.0001). 36 (19%) HA cases had a negative CPE screen before their first positive CPE test (10/36 (28%) were on admission). The median incidence of HA CPE per 100,000 patient-days at each hospital was 0.44 (IQR 0.15–0.68) (P < 0.0001).

Conclusion

A quarter of CPE cases in southern Ontario were HA and the incidence of HA cases is increasing. Most cases were admitted to >1 Ontario hospital. Strategies to control transmission are critical.

Disclosures

All authors: No reported disclosures.
525. Evaluation of Implementation of Guidelines for Carbapenem-resistant Enterobacteriaceae (CRE) Prevention Using the Consolidated Framework for Implementation Research (CFIR)
Authors: Goedken Cassie , Guihan Marylou , Brown Charnetta R , Ramanathan Swetha , Vivo Amanda , Fitzpatrick Margaret A , Perencevich Eli N , Rubin Michael , Reisinger Heather , Suda Katie J , Evans Martin , Evans Martin , Evans Charlesnika T
Published: October 2019

Background

Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing (CP) CRE are difficult to treat, resulting in a high mortality annually. In 2017, VA released guidelines for CRE/CP-CRE laboratory testing, prevention, and management. We used the Consolidated Framework for Implementation Research (CFIR) to understand factors influencing implementation of the CRE guideline at VA Medical Centers (VAMCs).

Methods

Between 9/17–8/18, 43 semi-structured interviews were conducted with Multi-Drug Resistant Organism Program Coordinators, laboratorians, physicians and infection preventionists from 29 geographically representative VAMCs of varying size and CP-CRE burden. Interviews addressed perceptions of guideline dissemination, laboratory testing, training, patient education, and IT support (e.g., CRE/CP-CRE flag, lab report and template). We analyzed transcripts using a consensus-based mixed deductive-inductive coding approach to identify CFIR constructs, best practices, recommendations/feedback and implementation challenges.

Results

95% of interviewees reported using VA CRE/CP-CRE guidelines, most (79%) with high confidence. Respondent comments (n = 798) were coded using CFIR constructs [Inner Setting (e.g., resources), (48%); Process (e.g., planning), (23%); Intervention Characteristics (e.g., VA guidelines) (17%); Outer Setting (e.g., patient needs) (6%); Characteristics of Individuals (e.g., self-efficacy) (6%)]. Interviewees also described Best Practices (15%) and Feedback/Recommendations (12%) including the need for improved lab testing/reporting, communication, contact isolation, staff training, patient education and cost.

Conclusion

Our results suggest sustained improvement in multiple areas to facilitate guideline implementation to identify, prevent, and manage CRE/CP-CRE are needed. This is critical because CRE/CP-CRE incidence and mortality rates are projected to increase.

Disclosures

All authors: No reported disclosures.
551. Burden of Illness in Carbapenem-Resistant Acinetobacter baumannii Infections in US Hospitals (2014 to 2018)
Authors: Pogue Jason M , Kanakamedala Hemanth , Zhou Yun , Cai Bin
Published: October 2019

Background

Infections caused by Acinetobacter baumannii present a challenge for treating physicians due to the high level of antimicrobial resistance. The current analysis compared the burden of illness in patients infected with carbapenem-resistant (CR) vs. -susceptible (CS) strains of A. baumannii.

Methods

Hospitalized adult patients with microbiologically confirmed A. baumannii infections (defined as a positive culture and receipt of antibiotics between 2 days prior to 3 days after the culture) included in the Premier Healthcare Database were retrospectively evaluated. Patient characteristics including demographics, comorbidities, time of infection onset and site of infection were assessed. Comparative outcomes between CR and CS patients assessed included in-hospital mortality, length of hospital stay (LOS), ICU LOS, and discharge status. Outcomes were also stratified by site of infection.

Results

A total of 3,471 patients admitted between January 1, 2014 and June 30, 2018 were included. Patients with CR strains of A. baumannii were older (62 vs. 59 years), more likely to have Charlson Comorbidity Index ≥3 (63.4% vs. 56.1%), more likely admitted from a healthcare origin (30.3% vs. 11.4%) and less likely to have the onset of infection within first 48 hours of hospitalization (58% vs. 69%) than those with CS strains. CR patients had increased inpatient mortality compared with CS patients (16.3% vs. 11.0%), driven primarily by patients with bloodstream infections (42.6% vs. 12.4%, respectively, P < 0.001). CR patients had a non-significantly increased median overall LOS from the onset of infection (9 vs. 8 days, P = 0.068), were more likely to be admitted to the ICU, and were significantly less likely to be discharged home (16% vs. 47%, P < 0.001). Hospitalization charges were considerably higher for CR patients (table). Readmission rates were high among CR patients and were similar to patients with CS infections.

Conclusion

Patients with CR strains of A. baumannii face a greater burden of illness compared with CS patients, experiencing increased mortality, ICU admission and LOS, and incur higher hospitalization charges. Furthermore, CR patients were less likely to be discharged home after admission.

Disclosures

All authors: No reported disclosures.