bluuebunny/crossref_metadata_2025 huggingface dataset:
222. Bloodstream Infections by Gram(−) Bacteria in Kidney Transplant Patients: Risk Factors, Incidence and Outcome; Bloodstream Infections by Gram(−) Bacteria in Kidney Transplant Patients: Risk Factors, Incidence and Outcome
Authors: Tsikala Vafea Maria , Basoulis Dimitris , Darema Maria , Deliolanis Ioannis , Pavlopoulou Ioanna , Pantazatou Angeliki , Sipsa Vasiliki , Daikos Georgios L , Boletis Ioannis , Psichogiou Mina
Published: October 2019

Background

Kidney transplant recipients are at increased risk for infections. The aims of this study were: i) to estimate the incidence of bloodstream infections (BSI) caused by Gram(−) bacteria in kidney transplant recipients, ii) to identify risk factors for BSI by multidrug-resistant Gram(−) bacteria, and iii) to identify predictors for outcome (death/loss of transplanted kidney).

Methods

We conducted a retrospective cohort study at the renal transplant unit (RTU) of a tertiary care hospital located in Athens, Greece, between September 2008 and September 2018. Kidney transplant recipients with Gram(−) BSIs were identified from the microbiology laboratory electronic records. Patient-, infection-, and treatment-related factors were extracted from the medical records. Species identification and susceptibility testing were performed by MicroScan automated system. The statistical analysis was performed using IBM SPSS Statistics v20.

Results

During the study period, 1962 kidney transplant patients were followed at our RTU. A total of 195 BSI episodes were recorded in 182 patients (male/female=97/85), with median (25th, 75th) age 57.2 (44, 64.9) years. The incidence of BSI was 1.393/100 patient-years. Median (25th, 75th) time interval between transplantation date and onset of BSI was 67.67 (8.3, 148) months. Escherichia coli was the most common cause (64.3%, 117/182), while the most common source of infection was urinary tract (70.9%, 129/182). 19.2% (53/182) of BSIs were caused by multidrug-resistant organisms (MDR). 6% (11/182) of patients died and 2.2% (4/182) were subjected to nephrectomy. Multivariate logistic regression showed that diabetes mellitus (odds ratio [OR] 7.714; 95% confidence interval [CI] 1.311–45.385), Pseudomonas aeruginosa BSI (OR 35.788; CI 3.3–388.182) and septic shock (OR 74.468; CI 3.513–1578.513) were predictors of an unfavorable outcome. Previous antibiotic use (OR 11.964; CI 2.686–53.293) and previous stay in Intensive Care Unit (OR 18.055; CI 1.046–311.536) were associated with MDR BSIs.

Conclusion

BSIs in kidney transplant recipients is a critical factor of morbidity and mortality. Recognizing the risk factors for unfavorable outcome and emergence of MDR bacteria could offer a significant advantage in early diagnosis and appropriate treatment.

Disclosures

All authors: No reported disclosures.
226. Nine-year Survey of Bloodstream Infections (BSIs) across Six Types of Solid-organ Transplant (SOT) at a Large University Medical Center
Authors: Buehrle Deanna , Clancy Cornelius J , Rivosecchi Ryan , Clarke Lloyd , Nguyen Minh-Hong
Published: October 2019

Background

BSIs are common in SOT patients. We surveyed BSIs across 6 types of SOT over 9 years at our center.

Methods

We conducted a retrospective study of BSI among patients transplanted from January 2010 to January 2019. Single blood cultures positive for coagulase-negative staphylococci, Corynebacterium, Bacillus, or Propionibacterium were excluded.

Results

3,358 patients underwent SOT, including kidney (K, 43%, 1432), lung (Lu, 23%, 778), liver (Li, 21%, 700), heart (H, 8%, 256), pancreas (P, 4%, 149), and small bowel/multivisceral (SB/MV 1%, 43). 16% (529) of patients had ≥1 episode of BSI. There were 770 BSIs; 14% (105/770) were recurrent. Median number of BSI was 1/patient (range: 1 to 7). BSI rates were highest among SB/MV patients (53%), followed by Lu (22%), Li (20%), P (15%), H (14%) and K patients (14%) (Figure 1). 20% (156), 24% (187) and 7% (52) of BSI occurred at ≤30 d, 31–180 d, and 181–365 d after SOT, respectively. BSI rates at ≤ and >180 d post-SOT were 3.6 and 0.65/1000 pt-d, respectively (P < 0.0001). Most common bacteria were Enterobacteriaceae (35%) and Enterococcus spp. (22%). Candida spp. accounted for 6% (49/770) of BSIs. Enterobactericeae were most common among intra-abdominal SOT patients, whereas Enterococcus and non-fermenting Gram-negatives were most common in Lu patients (Figure 2). 8% (65) of BSI was polymicrobial. From 2016 to 2018, 15% (14/96) of Enterobacteriaceae BSIs were multi-drug-resistant (MDR); 8% (8/96) were extensively drug resistant (XDR). 23% (3/13) of P. aeruginosa were MDR (all XDR). 70% (14/20) and 5% (1/20) of E. faecium and E. faecalis were vancomycin-resistant, respectively. Thirty-day mortality following BSI diagnosis was highest for H (31%), followed by Lu (15%), Li (10%), P (9%) and SB/MV (4%) patients. Patients with bacteremia had higher mortality than patients with no bacteremia (Figure 3).

Conclusion

BSIs are common after SOT, and associated with significant short- and long-term mortality. Almost half of BSIs occur within the first 6 months of SOT, when BSI rates are significantly higher than at later time points. Predominant BSI pathogens differ between SOT types; as such, empiric antimicrobial therapy decisions should be organ-specific. At our center, MDR and XDR Gram-negative bacteria and VRE are common; centers should use overall SOT and organ-specific antibiograms to drive empiric antimicrobial strategies.

Disclosures

All authors: No reported disclosures.
240. The Clinical Utility of Molecular Testing in the Diagnosis and Management of Infectious Diseases: Plasma-based Next-Generation Sequencing (PNGS)
Authors: Nomura Jim H , Tsai Townson
Published: October 2019

Background

Molecular diagnostic tests can provide microbiologic results rapidly and with greater sensitivity than traditional methods. However, these tests come with considerable costs, so thoughtful diagnostic stewardship is essential to ensure that resources and outcomes are optimized. We sought to evaluate the impact of PNGS testing on patient management.

Methods

From February 2017 to January 2019, physicians in our group ordered 164 PNGS tests (Karius, Redwood City CA) on 125 patients. A retrospective chart review was performed to determine the clinical indication and utility of the test.

Results

The assay failure rate was 4.9% (8/164). Positive (pos) results were noted in 34% (53/156), of which 23 (43.4%) represented false pos results; 28 were true pos (52.8%) but 2 were unnecessary (also had pos blood cultures). The most common reason for testing was to assess for Mycobacterium chimera (Mc) infection, representing 94 of 156 (60.3%) tests. Of the 21 patients with known Mc, only 10/21 had pos initial tests (47.6%); if patients with Mc localized to the sternum were excluded (8 patients), 76.9% with deep organ involvement had pos initial tests. Five patients with deep Mc infection had persistently pos results while on therapy; 4 of these had not had surgery; 1 was 6 months s/p valve replacement for Mc. The next most common indication was to r/o endocarditis in 18/156 (11.5%) and had an impact in 8/18 (44.4%), including 4 patients whose PNGS result identified a likely pathogen in culture negative endocarditis (CNE). Of the 62 tests done for non-Mc patients, 33.9% (21/62) were useful for management decisions. Among patients who eventually had a diagnosis made but had negative PNGS results included patients with Whipple’s (1), CNS infection (2), and fungal infections (5).

Conclusion

Overall, only 17.9% (28/156) of tests yielded true pos results. The most common reason was to evaluate for Mc infection. PNGS did not detect Mc in patients with proven local disease and was pos in >75% with deep/disseminated disease. However, a negative result did not exclude significant Mc infection. Repeat testing can be considered if clinical suspicion is high but should not be done before standard blood cultures are negative. While more than 60% of the non-Mc tests were not clinically useful, there was modest added utility where infection is high on the differential especially patients with CNE.

Disclosures

All authors: No reported disclosures.
241. Molecular patterns of Streptococcus agalactiae (GBS) Strains Associated with Different Clinical Syndromes: Early-Onset Disease in Neonates, Intrauterine Infection, and Vaginal Colonization, an Orthodox Jewish Community (OJC) Residing in Bney Brak
Authors: Shindler Yulia , Rahav Galia , Madar-Shapiro Liora , Abtibol Julia , Ravid Moti , Maor Yasmin
Published: October 2019

Background

Rectovaginal colonization during pregnancy with Group B Streptococcus (GBS) is a risk factor for early neonatal sepsis, and may also cause chorioamnionitis and fetal death. In Israel, the reported colonization rate in pregnant women is low, and therefore routine screening of pregnant women for GBS colonization is not recommended. We noticed higher rates of early-onset disease (EOD) due to GBS in newborns of women hospitalized in Maayaney Hayeshua Medical Center, which serves an Orthodox Jewish Community (OJC) in Israel. Therefore, our aim was to investigate molecular patterns of GBS strains from mothers and neonates hospitalized in Maayaney Hayeshua.

Methods

During 2017, GBS isolates were collected from asymptomatic pregnant women (280/1,074), neonates with EOD (n = 7), and intrauterine fetal death remains (IUFD) (n = 7). We serotyped isolates from vaginal carriage (n = 203), EOD (n = 7), IUFD (n = 7) and EOD isolates obtained from the Ministry of Health (n = 11). Multilocus sequence typing (MLST) was performed on isolates from asymptomatic pregnant women (n = 14), EOD (n = 7) and IUFD (n = 7). Antibiotic susceptibilities were determined.

Results

GBS carriage rate was 26.1%. In asymptomatic pregnant women the dominant serotype was VI [84 women (41.3%)], followed by III, IV and V in 32 (15.7%), 23 (11.3%) and 21 (10.3%) women, respectively. The dominant serotype in EOD was III [15/18 (83.3%)] and in IUFD VI [5 (71.4%)]. ST-17 was expressed mainly by serotype III, and was associated with EOD. ST-1, expressed mainly by serotype VI, was associated with IUFD. See Tables 1 and 2 and Figure 1. Resistance to erythromycin and clindamycin was 19.3% and 18.2% while resistance in invasive isolates was 45.5% to both antibiotics.

Conclusion

GBS vaginal colonization rate in an OJC was significantly higher than the reported carriage rate of 21.6% reported in Israeli pregnant women. Serotypes VI was dominant in carriage and in cases of IUFD while EOD was exclusively associated with serotype III. Resistance rates to erythromycin clindamycin were high, particularly in invasive disease. These results advocate routine GBS screening in this population and caution against empirical treatment with macrolides or clindamycin in penicillin-allergic women.

Disclosures

All authors: No reported disclosures.
256. Optimizing the Clinical Utilization of T2 Rapid Candida Panel at a Large Community Hospital
Authors: Thottacherry Elizabeth , Heard Gladys T , Steuber Taylor D , Hassoun Ali , Sawyer Adam J , Edwards Jonathan
Published: October 2019

Background

Candidemia is the fourth leading hospital-acquired bloodstream infection with an estimated mortality rate of 35%. Fungal blood cultures result in at least five days and fail to identify 40% of Candida infections. The T2 Candida Panel is a diagnostic test which utilizes whole blood to provide rapid detection of five Candida varieties. It has a 91% sensitivity and 99% specificity rate and enables physicians to initiate or de-escalate therapy rapidly, possibly decreasing mortality. However, practical utilization clinically has not been studied. Our aim is to evaluate the appropriate utilization of the T2 Candida Panel in a large community hospital.

Methods

A retrospective chart review of hospitalized with a T2 Candida Panel result from December 2015 to June 2018 was performed. The panel was restricted and could only be ordered by two specialties, Infectious Disease and Oncology. Baseline demographics and patient characteristics were collected. Endpoints assessed included patient outcomes, antifungal medication use, T2 Candida panel results, corresponding blood culture results, time to appropriate therapy and duration of therapy.

Results

A total of 628 T2 Candida panels resulted during the study period with 56.6% involving the intensive care setting. The average age was 59.5 years with 52.5% of the population being male. Of the total, 8.1% (n = 60) were positive. Only three patients had a positive fungal blood culture result with a negative T2 panel collected at the same time (sensitivity 94.3%, 95% CI 80.8–99.3; specificity 94.2%, 95% CI 91.4–96.3). 264 (42%) were ordered with concomitant antifungal therapy and 48.1% underwent de-escalation of therapy based on T2 result. The average time to de-escalation was 137 hours. Of the positive results, 40 (66.7%) had an antifungal ordered when the T2 panel was ordered and 30 (50%) were switched to appropriate therapy after T2 resulted in an average time of 11 hours.

Conclusion

Our data shows that while the T2 Candida Panel demonstrated faster and more sensitive results, there was still a considerable delay in achieving appropriate therapy. The variation in utilization of the T2 Candida Panel indicates that further intervention regarding appropriate use of the panel is required.

Disclosures

All authors: No reported disclosures.
277. Identification and Antifungal Susceptibility of Candida Species Isolated from Bloodstream Infections Over a 14-Year Period
Authors: Kline Ahnika , Andrew Clark , Lionakis Michail S , Zelazny Adrian
Published: October 2019

Background

Invasive infections caused by Candida species are associated with significant morbidity and mortality. Historically, C. albicans has been the predominant species recovered from patients with candidemia. However, the changing epidemiology of invasive candidiasis now includes more non-C. albicans species, which may exhibit intrinsic resistance or reduced susceptibility to antifungal agents used for therapeutic intervention. We sought to evaluate the epidemiology and susceptibility of invasive Candida ssp. isolates causing bloodstream infections at the NIH Clinical Center over a 14 year period.

Methods

Candida spp. isolates causing bloodstream infections between 2004 and 2018 were identified. Retrospective chart review was performed for infected patients in accordance with the IRB. All Candida isolates were recovered from frozen storage by plating onto Sabouraud Dextrose Agar, and isolate identities were confirmed by MALDI-TOF MS. Antifungal susceptibility testing was performed by broth microdilution and MICs were interpreted using current CLSI criteria.

Results

Between 2004–2018, we identified 98 unique clinical isolates from 77 patients with candidemia. Records from 75 of these patients were able to be reviewed, and the 30-day and 90-day mortalities were 24% and 52%, respectively. The average age at the time of culture positivity was 41.3 years (range 6.5 to 76.9 years). Thirty-one of the patients were female and 44 were male. C. albicans only constituted 18% of isolates (N = 18) and was the third-most prevalent Candida species identified behind C. parapsilosis (28%, N = 27) and C. glabrata (23%, N = 23), and followed by C. tropicalis (8%, N = 8) and C. krusei (6%, N = 6). As expected, fluconazole resistance was prevalent among C. glabrata (70%, N = 16) and C. krusei (100%, N = 6); however, a sizable proportion of C. parapsilosis (11%, N = 3), C. tropicalis (63%, N = 5) and C. albicans (22%, N = 4) strains also exhibited fluconazole resistance.

Conclusion

Our findings illustrate a high prevalence of non-C. albicans Candida spp. as the causative agents of bloodstream infections among patients at our institution. The clinical risk factors associated with the development of candidemia and azole resistance, as well as the molecular mechanisms of antifungal resistance are under investigation.

Disclosures

All authors: No reported disclosures.
281. Hypersensitivity Pneumonitis Diagnosed with Broad-Range PCR Testing after Exposure to Battarrea Mushroom Spores
Authors: Selby Laura , Jacobs Justin D , Brady Adam C
Published: October 2019

Background

Battarrea puffball mushrooms are found extensively worldwide and contain spore-containing sacs. Inhalation of the spores of similar mushrooms, such as Lycoperdon, have been implicated in cases of lycoperdonosis—a syndrome of hypersensitivity pneumonitis. We report a case of hypersensitivity pneumonitis confirmed to be secondary to Battarrea spore exposure diagnosed by broad-range PCR.

Methods

A 23-year-old homeless man with a history of methamphetamine use presented to the emergency department with a 2-week history of fevers, chills, productive cough, and malaise. He reported his symptoms began soon after eating a long-stemmed mushroom he found growing next to a building. He reported inhaling particles from the mushroom when he picked it up prior to eating it. He vomited within 1 hour of ingestion, and then had a worsening progression of cough and malaise over the following 2 weeks. In the emergency department, he was noted to have leukocytosis and mild elevation of transaminases. He required supplemental oxygen due to hypoxemia. CT scan of his chest demonstrated extensive bilateral nodular pulmonary infiltrates. He was admitted and started on treatment for community-acquired pneumonia. Over the next several days, he had worsening respiratory failure, and routine work up for infectious etiologies was unrevealing. To further investigate, bronchoscopy and bronchoalveolar lavage (BAL) was performed and routine bacterial, fungal and mycobacterial cultures and cytology with Gomori Methanamine-silver and acid-fast stains were negative. BAL fluid was sent for broad range DNA testing by PCR. Antibiotic therapy was stopped, and he was started on steroids to treat presumed hypersensitivity pneumonitis. He recovered rapidly and was discharged on a course of oral corticosteroids.

Results

After the patient was discharged, molecular testing of BAL fluid resulted with detection of Battarrea species DNA using 28s and ITS primer sets. DNA from no other pathogens was detected.

Conclusion

Identified through broad range DNA PCR testing, exposure to Battarrea mushroom spores may be a previously unreported cause of hypersensitivity pneumonitis. PCR testing should be considered in the workup of hypersensitivity pneumonitis with known or suspected exposure to mushroom spores.

Disclosures

All authors: No reported disclosures.
314. Healthcare Providers’ Views on HCV Testing and Counseling Among Sexual Partners of Hepatitis C-Infected Persons
Authors: Dunham Katherine , McDonald Jessica , Yousaf Anna , Barocas Joshua A , Neill Marguerite A , Noska Amanda J , Flanigan Timothy P
Published: October 2019

Background

Current hepatitis C virus (HCV) counseling guidelines from the Centers for Disease Control and Prevention (CDC) do not recommend that HCV-infected-patients notify their partners or encourage them to get tested. Because there is a small but present risk of HCV acquisition through sex, sexual partners should be encouraged to receive HCV counseling and testing. We aimed to assess healthcare professionals’ knowledge of and attitudes toward current counseling and testing recommendations for HCV-infected patients.

Methods

A 15-question, anonymous survey was designed and distributed to a convenience sample of healthcare providers (MDs, NPs, PAs) who work with Brown University or Boston University-affiliated hospitals. Questionnaires included demographic information as well as questions regarding providers’ current counseling practices and knowledge of current recommendations for HCV counseling. Descriptive statistics were used to analyze the survey data.

Results

Of the 55 respondents (a 20% response rate), 73% believed that current CDC HCV testing guidelines already recommend partners of HCV-infected patients be tested for HCV infection. Furthermore, 80% of respondents believed recommendations should be revisited to explicitly include that HCV-infected patients encourage their partners to get tested. When counseling patients with HCV, 44% of respondents reported they always ask whether the patient’s partners have been tested for HCV and 42% reported they sometimes do. Similarly, 42% reported they always suggest that the HCV-infected patient’s partners be tested for HCV. If sufficient resources were available, 75% of respondents reported that they would support active partner notification for HCV during an HCV outbreak situation and 72% said they would support active partner notification in a non-outbreak situation where there is still high HCV incidence.

Conclusion

Our survey shows that healthcare providers believe that current HCV-counseling and testing recommendations could be revisited, with specific attention given to the promotion of HCV testing for partners of HCV-infected patients.

Disclosures

All authors: No reported disclosures.
335. Antiretroviral Therapy Anchor-based Trends in Body Mass Index following Treatment Initiation among Military Personnel with HIV
Authors: Kline David , Daniels Colton , Xu Xiaohe , Sunil Thankam , Ganesan Anuradha , Agan Brian , Colombo Rhonda , Kronmann Karl , Blaylock Jason M , Okulicz Jason , Markelz Ana E
Published: October 2019

Background

Weight gain and obesity in people living with HIV have been associated with increased risk for non-AIDS-related comorbidities, and integrase strand transfer inhibitor (INSTI)-based regimens may lead to comparatively more weight gain than other regimens. We evaluated body mass index (BMI) following antiretroviral therapy (ART) initiation among participants in the US Military HIV Natural History Study (NHS).

Methods

Of 961 NHS participants started on initial ART between 2006–2017, 496 men who had available baseline BMI data and were virally suppressed (< 200 c/mL) at 1 and 2 years of follow-up were included (Tables 1 and 2). ART was categorized by anchor class to include INSTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Linear growth-curve modeling was used to predict BMI changes from ART initiation through 2 years of follow-up in participants stratified by baseline BMI (< 25 vs. ≥25 kg/m2) at ART start and anchor drug class. Demographic and HIV-related characteristics were analyzed as independent variables.

Results

Overall, the predicted BMI increased over 2 years regardless of baseline BMI (Table 3). There was a trend toward decreased BMI on ART for those with BMI ≥ 25 treated with a non-INSTI regimen (−0.63, P = 0.079). In participants with BMI < 25, all regimens were associated with overall gains in BMI except for those with high viral load (>100,000 c/mL) started on PI regimens (−1.61, P = 0.013). For those with BMI ≥ 25, only INSTI- and PI-based regimens were significantly associated with increased BMI (INSTI 0.54, P = 0.000; NNRTI 0.11, P = 0.174; PI 0.39, P = 0.006). Observed BMI increases for INSTI and PI regimens were also associated with increased time from HIV diagnosis to ART initiation (INSTI 0.35, P = 0.003; PI 0.44, P = 0.037). African Americans with BMI ≥ 25 on INSTIs had the greatest predicted gains in BMI (1.84, P = 0.007).

Conclusion

In our cohort of young military members with HIV infection, those with baseline BMI < 25 experienced BMI gains across all ART classes. Among those with baseline BMI ≥ 25, African Americans on INSTI regimens had the greatest BMI gains. Further studies are needed to determine whether NNRTI regimens should be considered in certain individuals at risk for INSTI-associated weight gain.

Disclosures

All authors: No reported disclosures.
360. Advanced Liver Disease in HIV/Hepatitis B Coinfected Patients: Associated with Race, Age, and Comorbidities
Authors: Go Gabriella , Vigil Karen J , Parisot Paul , Vu Trung , Taylor Barbara , Jain Mamta
Published: October 2019

Background

Hepatitis B virus (HBV) coinfection is common in people with HIV. Compared with HBV mono-infected individuals, those that are HIV/HBV coinfected show evidence of more rapid progression to advanced liver disease (ALD) and increased mortality rate. In this study, we identified characteristics in an HIV/HBV cohort associated with ALD.

Methods

We retrospectively examined an HIV/HBV coinfected cohort to determine the prevalence of ALD and its correlation with selected variables. Data were drawn from HIV and HBsAg+ patients at three HIV clinics in Houston, Dallas, and San Antonio, Texas. Those without chronic HBV were excluded. ALD was defined as cirrhosis, decompensation, and/or hepatocellular carcinoma, as determined by imaging. Variables included demographics, HIV risk factors, comorbidities, HBsAg loss, HepBeAg, CD4+ count, HBV DNA, and HIV RNA viral load. Bivariate analysis was performed using chi-square and student t-test as appropriate; a logistic regression model was used to identify independent associations among significant variables (STATA).

Results

Within those with HIV/HBV coinfection (n = 501), 89 (18%) met the criteria for ALD (92% male, 47% Black, 33% White, 16% Hispanic, 73% >40 years old). Amongst these (n = 89), significant differences were observed with race (P = 0.039), age (P = 0.001), patients identified as MSM/Bisexuals (P = 0.047), diabetes mellitus (DM) (P = 0.01) and hepatitis C virus (HCV) coinfection (P ≤ 0.001). Compared with Whites, Blacks are less likely to have ALD (95% CI 0.27, 0.79, P = 0.004), and those age 40–49 (95% CI 1.28, 10.92, P = 0.016) and >50 (95% CI 1.63, 15.54, P = 0.005) were more likely. The multivariate logistic regression analysis showed patients that are White race, age >50, have DM, and those with HCV coinfection had increased risk for ALD (Table 1). No differences were seen with gender, insurance, alcohol use, HBsAg loss, HepBeAg status or baseline CD4+ count, HBV DNA, HIV RNA, and AIDS.

Conclusion

Increased monitoring for the presence of ADL should be conducted in HIV/HBV coinfection. Particular attention and surveillance should be paid to those with the following risk factors: Whites, elder age (>50), and comorbidities of DM and HCV. These should be taken into consideration when approaching the development and treatment of ADL in HIV/HBV patients.

Disclosures

All authors: No reported disclosures.
374. Lymphogranuloma Venereum (LGV) Outbreak Among People Living with HIV (PLWH): Michigan, 2015–2018
Authors: Convery Christine , Kent James B
Published: October 2019

Background

Sexually transmitted infections (STIs) have increased in recent years both nationally and in Michigan. At the same time, HIV prevention is shifting toward intense efforts to “ending the epidemic.” Detecting and mitigating outbreaks, as well as monitoring co-infections in people living with HIV (PLWH), will be critical in these efforts. Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by a serovar of Chlamydia trachomatis and may present with proctitis, lymphadenopathy, or genital ulcers.

Methods

While not nationally reportable, LGV remains on the list of reportable conditions in Michigan. No cases were reported between 2009 and 2014, but from August 12, 2015 to December 4, 2018, 68 cases of LGV were identified in 66 patients and reported by providers and laboratories through the Michigan Disease Surveillance System (MDSS). These reported cases were analyzed by specimen collection date and matched to other communicable disease databases for HIV co-infection status and STI history using SAS 9.4.

Results

The outbreak was local to Southeast Michigan where all but three patients resided; 72% cases lived in Detroit (Figure 1). 94% of cases were co-infected with HIV, including 4 who were co-diagnosed within 30 days of LGV diagnosis. Among the 60 cases of PLWH (excluding co-diagnoses), 62% were virally suppressed (VS) and 32% were in care but not suppressed at the time of LGV diagnosis. The majority (88%) of outbreak patients had between 1 and 7 additional bacterial STIs in the two years prior to LGV. All reported cases were men who have sex with men (MSM) with two patients also reporting injection drug use (MSM/IDU).

Conclusion

Testing for LGV is not routine and in some settings not available so there are likely unreported cases missing from this outbreak analysis. HIV care outcomes differed from statewide estimates with outbreak patients more likely to be receiving care but not sufficiently engaged compared with all PLWH (Figure 2). A high proportion of cases with additional STI history combined with lower than average VS rate means transmission of HIV is likely. This highlights a need to integrate HIV care support with STI services. Additional analyses of HIV co-infection with syphilis or other STIs are needed to further inform these strategies.

Disclosures

All authors: No reported disclosures.
381. Clinical Outcome of Polymicrobial Prosthetic Joint Infection Managed with Debridement, Antibiotics, and Implant Retention (DAIR)
Authors: Hooshmand Babak , Youssef Dima , Riederer Kathleen M , Szpunar Susan M , Bhargava Ashish
Published: October 2019

Background

Polymicrobial (PM) prosthetic joint infections (PJIs) account for 4% to 37% of all PJIs. There is limited literature on surgical debridement, antibiotics and implant retention (DAIR) in PMPJIs. We aimed to assess clinical outcomes of PMPJIs managed with DAIR.

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

Twenty-six PMPJIs managed with DAIR were identified. Mean age of the infected patients was 66 years. 18 (69%) patients were female and 19 (73%) were caucasians. Infected sites were hip in 15 (58%), knee in 10 (38%) and ankle in 1 (4%) patient. 22 (85%) patients had osteoarthritis, 3 (12%) had diabetes, 3 (12%) were on steroids and 1 (4%) had rheumatoid arthritis. Symptom onset of less than a week was noted in 14 (58%) and 3 or more weeks in 8 (31%) patients. Pain, swelling and drainage were present in 21 (81%), 13 (50%) and 18 (69%) cases. Fever on admission was noted in 7 (27%) patients. 11 (42%) patients were re-admitted in the following 12 months after DAIR. 2 (19%) patients developed superficial surgical site infection (SSI) while 9 (81%) had deep SSI. Implant removal was needed in 6 (55%) patients. 5 (2 superficial and 3 deep) patients required further debridement and antibiotics. 5 (19%) had good outcome with 3–6 months of antibiotics. 3 (12%) patients required long-term chronic suppressive therapy. One patient died from a cardiac event during follow-up.

Conclusion

In our study, PMPJIs managed with DAIR had high readmission rates and deep surgical site infections. DAIR failure, noted in 23% of our cases, required implant removal within 12 months of follow-up.

Disclosures

All authors: No reported disclosures.
387. A Rare Manifestation of a Common Disease: Tenosynovitis Associated with Clostridium difficile: Case Report and Review of Literature
Authors: Josephson Greta M , Ajmal Saira R
Published: October 2019

Background

Reactive arthritis typically develops following enteric or genitourinary infection. The most common offending pathogens are Chlamydia, Salmonella, Shigella, Yersinia and Campylobacter. We report a unique case of a patient with tenosynovitis attributed to Clostridium difficile (C. difficile), and review of the literature.

Methods

We searched PubMed for “reactive arthritis” and “C. difficile” and found 53 cases. Two additional cases were excluded as they were published in French.

Results

An 18-year-old healthy male presented with nine days of abdominal pain and diarrhea, and two days of pain and swelling of bilateral fingers with an erythematous/ecchymotic rash over the second and third digits. Four weeks prior to symptom onset he received antibiotics for streptococcal pharyngitis. On presentation he had diffuse abdominal tenderness and edema of the PIP/DIP joints with tenderness throughout the phalangeal soft tissue, consistent with tenosynovitis. He had a leukocyte count of 33.0 thou/ μL and C-reactive protein of 12.0 mg/dL (normal < 1.0 mg/dL). C. difficile toxin PCR was positive, toxin EIA was negative. CT scan of the abdomen/pelvis demonstrated mural thickening consistent with extensive severe colitis. He received 14 days of oral vancomycin, with complete symptom resolution, including the tenosynovitis. Our literature review revealed 22.6% (12/53) of cases had involvement of hands, although all also had involvement of other joints. Our patient’s isolated tenosynovitis of bilateral hands is unique, and has only been reported once prior to our knowledge. Literature suggests treatment of the underlying C. difficile infection should result in rapid clinical improvement of tenosynovitis symptoms, as in our patient.

Conclusion

C. difficile continues to pose a significant threat to health and burden on the healthcare system. The association of reactive arthritis and C. difficile was first reported in 1976, with only 53 subsequent cases reported. Reactive arthritis classically presents as asymmetrical oligo- or polyarthritis involving lower extremities or large joints. Our case demonstrates isolated tenosynovitis of the hands may also be a possible presentation. Given the continued rise of C. difficile, it is imperative that this pathogen is considered in such cases.

Disclosures

All authors: No reported disclosures.
390. Treatment and Outcome of Methicillin-Resistant Staphylococcus aureus Hip and Knee Prosthetic Joint Infection
Authors: Henry Michael , Carli Alberto V , Kapadia Milan , Chiu Yu-fen , Brause Barry , Miller Andy O
Published: October 2019

Background

Methicillin-resistant Staphylococcus aureus (MRSA) total hip and knee prosthetic joint infections (PJI) can be highly morbid and difficult to treat. Other clinical factors notwithstanding, explantation is usually recommended, although comparative treatment data are lacking. We sought to compare the success of implant retention to two-stage exchange in MRSA-infected PJI to better understand treatment options in this difficult cohort.

Methods

A retrospective cohort of hip and knee PJIs from 2009 to 2016 were identified by ICD code and surgical treatment. All cases met MSIS criteria for PJI, and had culture-confirmed MRSA from synovial or intra-articular tissue culture. PJIs were either treated with exchange arthroplasty or debridement with antibiotic and implant retention (DAIR). Success was defined as no further surgical treatment for infection at two years. Kaplan–Meier estimates were used to calculate the 2-year survival rate free from treatment failure. Univariate logistic regression was performed to identify risk factors associated with treatment failure.

Results

65 MRSA PJIs were identified with 42 undergoing explantation and 23 undergoing DAIR. Demographics, Charlson comorbidities, infection type (early post-operative, hematogenous or late chronic), and history of prior PJI were not significantly different between treatment groups. Survivorship at two years was 75% (95% confidence interval [CI] 61–88%) for exchange compared with 29% (95% CI 10–48%) for DAIR, P = 0.0002. Within the exchange group, knee PJIs were more likely to fail than hip PJI (odds ratio [OR] 7.1, CI 1.3–38, P = 0.02), and patients with diabetes were more likely to fail (OR 17, CI 1.6–178, P = 0.02).

Conclusion

MRSA PJIs treated with DAIR have worse outcomes than those treated with prosthesis exchange. Further investigation is needed to identify predictors of DAIR success, to optimize surgical treatment choice, and to improve outcomes of these difficult infections.

Disclosures

All authors: No reported disclosures.
400. Comparison of Tolerance and Microbiological Efficacy of Cefepime and Piperacillin/Tazobactam in Combination with Vancomycin as Empirical Antimicrobial Therapy of Prosthetic Joint Infection: A Propensity-Matched Cohort Study
Authors: Triffault-Fillit Claire , Mabrut Eugenie , Corbin Karine , Becker Agathe , Braun Evelyne , Tod Michel , Goutelle Sylvain , Henri Fessy Michel , Dupieux Celine , Laurent Frederic , Lustig Sebastien , Chidiac Christian , Ferry Tristan , Valour Florent
Published: October 2019

Background

The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading to propose cefepime as an alternative since 2017 in our reference center. The present study compared microbiological efficacy and tolerance of these two EAT strategies.

Methods

All adult patients with PJI empirically treated by vancomycin-cefepime (n = 89) were enrolled in a prospective observational study, and matched with vancomycin-piperacillin/tazobactam-treated historical controls (n = 89) according to a propensity score including age, baseline renal function and concomitant use of other nephrotoxics. The two groups were compared using Kaplan–Meier curve analysis and non-parametric tests (Fisher exact test and Mann–Whitney U-test) regarding: (i) the proportion efficacious empirical regimen (i.e., at least one of the two molecules active against the identified organism(s) based on in vitro susceptibility testing); and (ii) the incidence of empirical therapy-related adverse events (AE), classified according to the Common terminology criteria for AE (CTCAE).

Results

Among the 146 (82.0%) documented infections, the EAT was considered as efficacious in 77 (98.7%) and 65 (98.5%) of the piperacillin–tazobactam and cefepim-treated patients, respectively (P = 1.000). The rate of AE, and in particular AKI, was significantly higher in the vancomycin–piperacillin/tazobactam (n = 27 [30.3%] and 23 [25.8%%]) compared with the vancomycin-cefepim (n = 13 [14.6%] and 6 [6.7%]) group (P = 0.019 and <0.001, respectively; figure), leading to a premature EAT discontinuation in 20 (22.5%) and 5 (5.6%) patients (P = 0.002). Of note, no significant differences were observed between the two groups regarding sex (91 males; 51.1%), median age (68-year-old; IQR, 59.3–75), main comorbidities including baseline renal function and proportion of patients receiving other nephrotoxics, and vancomycin plasmatic overload.

Conclusion

The empirical use of vancomycin-cefepim in PJI was as efficient as vancomycin–piperacillin/tazobactam, and was associated with a significantly lower incidence of AKI.

Disclosures

All authors: No reported disclosures.
406. Cloning Antibodies Against Kawasaki Disease from Acute Plasmablast Responses
Authors: Baron Sarah , Sojar Hakimuddin T , Hicar Mark D
Published: October 2019

Background

Kawasaki Disease (KD) is a childhood vasculitis, marked by prolonged fevers and coronary artery inflammation/aneurysms in near one-quarter of those untreated. The cause remains unknown; however, epidemiologic and demographic data support a single preceding infectious agent may lead to KD. Plasmablasts (PBs) are a stage of transitional B-cells that lead to plasma cells, the long-lived antibody-producing cells of the bone marrow. After initial infection, peripherally circulating PB populations are enriched for cells with antibodies against the preceding infection. We have recently published data showing children with KD have similar PB responses to children with infections. We sought to define the antibody characteristics, including clonality, of these PBs during KD.

Methods

We used antibody repertoire next-generation sequencing to characterize memory and PB populations. Additionally, pairing of heavy and light chains was performed with Chromium Single Cell Gene Expression (10x Genomics, Pleasanton, CA) using the Human B cell Single Cell V(D)J Enrichment Kit.

Results

From subject 24, antibody sequences using VH4-34 and a 19 amino acid length complementarity determining region 3 showed a massive expansion between day 4 and 6 of fever. Chromium single-cell sequencing produced over 946 heavy and light chain paired sequences. Sequence comparison showed 40% of sequences demonstrated markers of clonal expansion, which represented 100 clonal groups. Seven other KD subjects are being processed and comparative analysis will be presented.

Conclusion

This clonal expansion within plasmablast populations supports that Kawasaki disease is caused by an infection. Antigen targeting of these monoclonal antibodies is currently being explored.

Disclosures

All authors: No reported disclosures.
412. Host Response Biomarkers Predict Clinical Failure in Patients with Staphylococcus aureus Bacteremia (SAB) Treated with Flucloxacillin (FLU) or Vancomycin (VAN)
Authors: Aycock Anna , Holmes Natasha , Howden Benjamin , Hayney Mary , Sakoulas George , Rose Warren
Published: October 2019

Background

Imbalance among innate mediators such as IL-1β, IL-10, and TNF-α portends poor outcomes of persistence and death in patients with SAB. Previous studies did not consider the role of antibiotic treatment in this important host–pathogen relationship. In this study of SAB, we determined cytokine signatures that correlate with the composite endpoint of clinical failure (bacteremia duration >4 days or 30-day mortality) in Australian patients treated with FLU or VAN.

Methods

Sera from 86 patients with SAB (24.4% MRSA) were obtained from a clinical study of patients treated with FLU or VAN. All of the patient samples were collected at clinical presentation (day 0 or day 1 of infection) and were treated with FLU or VAN throughout. Patients were classified into either clinical success (CS = 68) or clinical failure (CF = 18), defined as death or prolonged bacteremia >4 days. Patient demographic and infection characteristics were collected. A 10-multiplex TH1/TH2 cytokine analysis was performed using electrochemoluminescence with the Meso-Scale Discovery platform analyzed by Mann–Whitney U.

Results

Patients’ median values were significantly elevated and above the normal range in CF for IL-1β (P = 0.029), IL-10 (P = 0.018), TNF-α (P = 0.042), and IL-6 (P = 0.006) (figure). Epidural abscess source was associated with CF, but no other host or pathogen characteristics correlated to outcome. Patients infected with isolates with VAN MIC = 2 mg/L (by Etest and broth dilution) had lower concentrations of IL-1β and IL-10 (P = 1.5 mg/L. In ROC analysis, IL-1β, IL-10, TNF, and IL-6 were higher sensitivity and specificity predictors of CF (AUC 0.65–0.71; P = 0.05).

Conclusion

A suboptimal host immune response to SAB at presentation predicts adverse clinical outcomes. IL-10, TNF-α, and IL-6 serum concentrations appear to reflect immunopathology in patients with SAB. These predictive markers may be considered in therapeutic clinical decision-making, such as escalation of alternative therapies in high-risk patients and/or de-escalation treatment in low-risk patients. These data offer steps toward further refining therapeutic precision for patients with SAB beyond the standard clinical or microbiological metrics that are employed in current practice.

Disclosures

All authors: No reported disclosures.
414. Developing Digital Phenotypes of Primary Immune Deficiencies Using Machine Learning on a Large Electronic Health Record Database
Authors: Meister Leo , Zerbe Christa , Notarangelo Luigi D , Kadri Sameer S , Rebecca Prevots D , Ricotta Emily
Published: October 2019

Background

More than 350 genetic disorders cause immune deficiencies; given the rarity of these conditions, in-depth study of infections associated with primary immune deficiencies (PID) requires extremely large sample sizes from broad populations. Using a large electronic health record (EHR) dataset, we linked clinical and microbiologic data to develop digital phenotypes for PID.

Methods

Using the Cerner HealthFacts EHR dataset from 2009 to 2017 we extracted clinical and microbiologic data for hospitalizations from patients <18 years old with ICD9/10 PID diagnoses and ≥1 positive culture for infection. Machine learning models were used to identify key features to predict PID diagnosis. Features included patient and hospitalization characteristics; infectious agent and infection site; and selected comorbidities. Model validation was done using the area under the receiver operating characteristic (AUC) curve.

Results

Overall 1316 patients with a PID were identified (Table 1). The 10 most common pathogens identified by PID are listed in Table 2. The models classified DiGeorge syndrome (positive predictive value 49%), functional disorders of polymorphonuclear neutrophils (PMN) (PPV 43%), and common variable immunodeficiency (CVID) (PPV 47%) better than combined immunodeficiency (CID) (PPV 20%); the overall true positive rate was 47% with an AUC of 0.73. Predictive features for each PID were as follows: CVID—having enteritis, hypertension, and pneumonia (Figure 1a); PMN—having hypoxia and hypertension (Figure 1b); DiGeorge syndrome—having congenital deformities and not having hypertension (Figure 1c); CID—finding Staphylococcus aureus in a wound or Escherichia coli in the blood were predictive of CID (Figure 1d).

Conclusion

Early models demonstrate some discrimination, specifically for more common PIDs (CVID) and those with highly identifying factors (DiGeorge syndrome). These models can be improved by including a wider array of clinical data, and they provide a first look at a new methodology to digitally phenotype PIDs for future diagnostic use.

Disclosures

All authors: No reported disclosures.
420. Prevalence of Oropharyngeal Meningococcal Carriage in an Urban STD Clinic
Authors: Turner Abigail N , Carter Alexandria , Tzeng Yih-Ling , Brown Morgan , Stephens David , Snyder Brandon , Prince Devlin , Bazan Jose A
Published: October 2019

Background

Neisseria meningitidis (Nm) can cause invasive disease, but it also asymptomatically colonizes the pharynx in approximately 10% of the general population. Older studies have reported higher carriage rates (>30%) among individuals attending sexually transmitted disease (STD) clinics. This study examined the prevalence of oropharyngeal Nm carriage in STD clinic attendees in Columbus, Ohio.

Methods

Per normal procedures, all patients presenting for care in the STD clinic who report oral sex in the last year are screened for oropharyngeal Neisseria gonorrhoeae (Ng) using nucleic acid amplification testing (NAAT). For the same patients, we also initiate cultures using media selective for Neisseria spp. Analytical Profile Index Neisseria-Haemophilus (API NH) and Nm-specific PCR screening is performed on colonies with oxidase-positive Gram-negative diplococci to distinguish between Ng and Nm. For this study, we then performed PCR-based genogrouping on confirmed Nm isolates.

Results

Between July 2018 and March 2019, oropharyngeal screening occurred at 5,015 patient visits and oropharyngeal Nm was detected at 163 visits (3.3%). Nm-positive individuals were primarily male (69.9%), Caucasian (62.6%), with non-Hispanic ethnicity (98.8%). The median age was 27 years and 5.5% were HIV-positive. Among male cases, 49.1% reported sex with men; among women, 98.0% reported sex with men. Meningococcal vaccination status was unknown for 71.2%, but 26.4% had documentation of prior MenACWY vaccination and 2.3% had prior MenB vaccination. Among the 163 cases, genogroup distribution was 23.9% B, 10.4% E, 9.8% Z, 3.1% C, 0.0% W, 0.0% Y, and 39.3% capsule null locus. For 13.5%, the selected screening approach could not determine genogroup.

Conclusion

In STD clinic patients reporting recent oral sex, we found a much lower prevalence of oropharyngeal Nm carriage compared with what has been reported historically for similar populations. While NmB was the most common capsular type identified by genogrouping, almost 40% of Nm isolates contained the capsule null locus, making them unable to express capsule. Additional studies should evaluate the effect of Nm vaccination programs on carriage among STD-clinic attendees.

Disclosures

All authors: No reported disclosures.