bluuebunny/crossref_metadata_2025 huggingface dataset:
732. Evaulation of Micafungin Treatment at Pediatric Patients: A cross-sectional Study from Tertiary Pediatric Centre
Authors: Arıkan Kamile , Bayram Nuri , devrim İlker , Akaslan-Kara Ayküke
Published: January 2021

Background

Micafungin is one of three currently available echinocandin for treatment of candidiasis and candidemia.

Methods

Children who were treated for micafungin for possible or proven invasive Candidia infection between May 2017 and October 2019 were included.

Results

In this cross-sectional study, totally 78 children with a median age of 3 months (8 days -17 years), 50 (64.1%, F/M: 0.56) male were included. Thirty four (43.6%) patients were neonate, 26 (76 %) of them were premature. Thirty seven patients (47.4%) received micafungin for candidemia and 41 (52.6%) patients received micafungin empirically for IC. Twelve (32.4%) Candida spp cultured were C. albicans, the rest twenty five (67.6%) Candida spp were non-albicans Candida spp. The most commonly cultured Candida spp was Candida parapsilosis (C. parapsilosis) (n=13) followed by C. albicans (n=12), C. glabrata (n=3), C. tropicalis (n=3), C. guilliermondii (n=3), C. krusei (n=2) respectively. Resistance rate of C. parapsilosis (n=13) isolates to fluconazole, voriconazole, amphotericin B, caspofungin, micafungin were as follows respectively; 66.7%, 100%, 69.2%, 90.9%, 37.5% respectively. Resistance rate of C. albicans (n=11) isolates to fluconazole, voriconazole, amphotericin B, caspofungin, micafungin were as follows respectively; 50%, 50%, 12.5%, 42.9%, 0% respectively. None of the C. tropicalis, C. guilliermondii and C. krusei isolates were resistant to micafungin. Culture negativity could not be achieved at the end of 14th day of micafungin treatment in the 15 (16.9%) candidemia episodes. The most commonly isolated Candida spp in patients with treatment failure was C. parapsilosis (n=7), the other species were; C. albicans (n=5), C. guilliermondii (n=1), C. tropicalis (n=1) and C. tropicalis and C. guilliermondii coinfection (n=1) respectively. Median serum AST, ALT and creatinin levels didn’t increase during and at the end of micafungin therapy. None of these patients had experienced an anormal kidney or liver function tests due to micafungin usage.

Characteristics of patients who received micafungin.and cultured Candida spp

Antifungal resistance patterns of Candida spp.

Laboratory change before and after micafungin treatment

Conclusion

Increase in fluconazole resistant Candida spp makes micafungin a reasonable and effective choice for suspected or proven invasive candidiasis

Disclosures

All Authors: No reported disclosures
737. A Descriptive Analysis of Fluconazole Utilization at Two Academic Medical Centers in the Valley Fever Corridor of Arizona
Authors: Hayes Justin , Matthias Kathryn , Villanueva Juan , Nix David
Published: January 2021

Background

Fluconazole (fluc) is a common antifungal used at hospitals and is an important target for antimicrobial stewardship (AS). Fluc is also used for management of coccidioidomycosis (C). The objective of our study was to describe fluc prescribing patterns at two academic centers in Arizona.

Methods

We conducted a retrospective analysis of fluc usage in adult patients. One month from each quarter in a one-year period (November 2017-November 2018) was selected (4 months in total). All adult patients that received fluc at Hospital A and Hospital B in the selected months were identified. Patient demographic information and Charlson comorbidity index (CCI) to quantify the degree of comorbidity were collected. We then analyzed patients in the study by defining the fluc usage as directed towards C management or non-C management (e.g., candidiasis). In the C management group, we characterized the initial fluc dose during the patient’s course as directed for empiric, targeted, or prophylaxis treatment. Finally, we performed further analysis of the empiric C group. The study received IRB approval from our institution.

Results

During our study period, 1239 patients were included in the analysis. Patient information is shown in Table 1. Overall, most of the fluc usage was directed towards C management (63.5%, 787/1239). A significant amount of that usage was directed towards C prophylaxis at both Hospital A and B (67.4% (234/347) and 75% (330/440), respectively). In addition, fluc usage directed towards empiric C management was higher at Hospital A versus Hospital B (18.4% (64/347) versus 9.5% (42/440), respectively). Further patient data for the empiric C group is shown in Table 2.

Conclusion

We report the results of a descriptive study that demonstrate that 63.5% of fluc usage in adults at two academic medical centers in Arizona was directed for C management. In addition to traditional fluc targets for AS, our study highlights C prophylaxis in solid organ transplant recipients and empiric C management as AS targets in endemic regions. These targets are especially important due to the risk for selection of azole-resistant Candida species and invasive molds with increased antifungal exposure.

Disclosures

All Authors: No reported disclosures
738. A Novel Molecular Diagnostic Assay for Identification of Fungal Pathogens
Authors: Matzko Michelle E , Martinsen Melanie A , Sephton-Clark Poppy , Cuomo Christina , Bhattacharyya Roby P
Published: January 2021

Background

A rapid and accurate diagnostic method for invasive fungal infections remains a critical clinical need. We recently reported a rapid molecular method for bacterial species identification directly from clinical samples that targets highly abundant ribosomal RNA on a multiplexed hybridization platform called NanoString. Here we report an adaptation of this assay that accurately distinguishes common fungal pathogens with limit of detection at a single yeast cell.

Methods

Building on our bacterial approach, we computationally designed specific hybridization probes targeting species-specific variable regions of fungal 18S and 28S rRNA from 12 clinically relevant fungi: Aspergillus fumigatus, Cryptococcus neoformans, and 10 Candida species, including Candida auris. Following mechanical lysis of crude specimens, fungi were detected from laboratory culture or artificial cerebrospinal fluid via multiplexed hybridization on a NanoString (Seattle, WA) instrument which yielded results within 7 hours from sample collection. Assay sensitivity was probed using serial dilutions of lysed C. albicans in culture, and cell-equivalents were confirmed by plating.

Results

Our hybridization probes targeting fungal rRNA specifically recognized all species tested to date: A. fumigatus, C. neoformans, and C. albicans with no cross-reactivity (Fig 1a). Serial dilutions of C. albicans lysate demonstrated a limit of detection around 0.1 cell equivalents without rRNA amplification (Fig 1b), capitalizing on the intrinsic abundance of rRNA in fungal cells.

Figure 1.

Conclusion

We adapted a rapid, ultrasensitive hybridization-based diagnostic assay that has proven successful in bacteria, to fungi. Here we show the accurate detection of Aspergillus, Cryptococcus, and Candida species, including a computational design that will enable the distinction of 10 different Candida species, including C. auris, within hours from clinical specimen collection.

Disclosures

All Authors: No reported disclosures
742. Breakthrough Invasive Fungal Infections with Isavuconazonium Sulfate versus Voriconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia (AML) who Received Induction Chemotherapy
Authors: Singam Hareesh v , Pasikhova Yanina , Quilitz Rod , Greene John N , Baluch Aliyah
Published: January 2021

Background

Fungal infections in patients with hematologic malignancies are associated with high mortality. Primary antifungal prophylaxis has been shown to be a more effective strategy than treating a documented infection. This retrospective analysis aims to compare the rates of breakthrough invasive fungal infections in patients with acute myeloid leukemia (AML) who received induction chemotherapy and were prescribed voriconazole (Vori) or isavuconazonium (Isv) for primary antifungal prophylaxis.

The European Organization for Research and Treatment of Cancer/ Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to categorize incidence of breakthrough invasive fungal infections bIFI into ‘possible’, ‘probable’ or ‘definite’ groups who required treatment with liposomal amphotericin B, echinocandin, and/or different triazole.

Methods

This is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML. These patients received either Vori or Isv sulfate as the primary antifungal prophylaxis at Moffitt Cancer Center between July 2017 and June 2019. Patients who were over 18 years old and received at least 10 days of uninterrupted primary antifungal prophylaxis with either Vori or Isv sulfate were included in the study. Patients with a history of stem cell or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or who received systematic antifungal, other than fluconazole, therapy within 30 days to induction chemotherapy were excluded.

Results

250 patients were screened for the study and out of which 118 patients met the above criteria. There was a 20.2% (18/89) break through rate of fungal infections in the Vori arm and 17.2% (5/29) in the Isv arm. In the Vori arm there were 15 possible bIFIs, 3 probable bIFIs and 0 definite bIFIs. In the Isv arm there are 2 possible bIFIs, 2 probable bIFIs and 1 definite bIFIs.

Conclusion

There is no significant statistical difference (Using the Fisher Exact test statistic p=1) between the Isv and Vori in patients who received these agents for primary fungal prophylaxis for induction chemotherapy for AML at Moffitt Cancer Center between July 2017 - June 2019.

Disclosures

Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)
743. Characteristics of Candidemia in a Coccidioidomycosis Endemic Region: The impact of Increased Azole Use in the Selection of Candida species
Authors: Al-Obaidi Mohanad , Marquez Jose , Afghan Abaseen , Zangeneh Tirdad
Published: January 2021

Background

The incidence of invasive candidiasis secondary to non-albicans Candida species is on the rise. In Arizona, azoles are used for coccidioidomycosis treatment and prophylaxis in immunosuppressed population. Therefore, we intended to describe the characteristics and outcomes of non-albicans Candidemia in our area.

Methods

We conducted an IRB approved multicenter study evaluating patients from October 1, 2017 to January 1, 2020. Patient demographics, medical history, procedures, antifungal use, and laboratory data were collected. Episode per patient was included in the statistical analysis.

Results

In the study period, there were 145 patients with 151 candidemia episodes. For the episode-per-patient, median age was 51 (IQR 37-62), 45% were female, and 86% were Caucasian. 10% had a history of transplantation (40% HSCT and 60% SOT), and 22.5% had a history of cancer. 78% had another concomitant systemic infection. 4/80 (5%) and 12/102 (12%) had infective endocarditis. Only 5 (3.3%) had a history of coccidioidomycosis and 37 (24.5%) had exposure to azole therapy in the prior 3 months. 60% of the candidemia episodes were due to non-albicans Candida species, 27/37 (73%) had a prior history of azole therapy, 12/15 (80%) were transplant recipients, and 23/34 (80%) had cancer. The majority (71%) of patients initially received an echinocandin without a significant difference in mortality. Of all the admission episodes, there were 45/151 (29%) deaths and 7/151 (4.5%) were discharged to hospice. Not removing central catheters was associated with 60% of deaths (P=0.002). Infectious diseases consult was associated with lower mortality (OR 0.25, 95% CI 0.087-0 .70) and higher rates of catheter removal (OR 8, 95% 2.2-29.5). There was no difference in mortality between non-albicans versus albicans Candidemia (28.6% vs. 32%, P=0.7).

Conclusion

Our study found higher rates of non-albicans Candidemia that are more eminent in transplant recipients and those with prior azole use, but this was not statistically significant. The removal of the central line and ID consultations was associated with a significant reduction in mortality. In Coccidioidomycosis endemic regions, the risk of non-albicans candida infections can be higher with the use of azoles; however, further studies are recommended.

Disclosures

All Authors: No reported disclosures
744. Clinical Performance of Real-time PCR in the Diagnosis of Pneumocystis jirovecii Pneumonia compared with Immunofluorescence Assay
Authors: Veintimilla Cristina , Alvarez-Uria Ana , Martin-Rabadan Pablo , Alcala Luis , Muñoz Patricia , Marin Mercedes
Published: January 2021

Background

The laboratory diagnosis of Pneumocystis jirovecii pneumonia (PJP) has been traditionally based on microscopy techniques, which have suboptimal sensitivity and depends on the experience and skills of the microbiologist. Molecular detection assays based in PCR (Polymerase chain reaction) could improve sensitivity.

Our aim was to evaluate the utility of real-time PCR in the diagnosis of PJP compared with IFA (Immunofluorescence assay) performed in different respiratory samples of patients with PJP suspicion for routine use in a clinical laboratory setting.

Methods

From September 2015 to April 2018, we studied by a real-time PCR targeting the large subunit of rRNA gene of P. jirovecii (PJ-PCR RealCycler PJIR kit Progenie Molecular) and Immunofluorescence assay (MONOFLUO P. carinii IFA BioRad) in all respiratory samples received for microbiological diagnosis of PJP. The definite clinical diagnosis of PJP was established by infectious disease physicians considering symptoms, radiological and laboratory findings.

Results

Overall, 302 samples were included (182 bronchoalveolar lavage, 67 sputum, 53 tracheal aspirates). PJ-PCR was positive in 51 (16.9%) and IFA in 11 (3.6%) of the patients with PJP. There were not IFA positive/PCR negative samples. Sensitivity, specificity, PPV and NPV for IFA were 26% (95%CI 15.9-39.6%), 100% (95%CI 98.5-100%), 100% (95% CI 77.2-100%) and 87.2% (95% CI 82.6-90.6%). Whereas, sensitivity, specificity, PPV and NPV for PCR was 92% (95%CI 81.2-96.8%), 98% (95% CI 95.4-99.2%), 90.2% (95% CI 79.0-95.7%) and 98.4% (95% CI 96.0-99.4%).

PJ-PCR had sensitivity > 80% and specificity > 90% in all type of samples included.

A definitive diagnosis of PJP was considered in 50 (16.6%) patients, including 4 (1.3%) cases with negative PJ-PCR. Five cases (9.8%) with positive PJ-PCR were considered as colonization.

Conclusion

P. jirovecii PCR improves the sensitivity and NPV of PJP diagnosis respecting to IFA, regardless of respiratory sample type. Our results suggest that Microbiology laboratories should use PCR techniques to diagnose PJP better than IFA.

Disclosures

All Authors: No reported disclosures
745. Combination Treatment of Liposomal Amphotericin B and Isavuconazole is Synergistic in Treating Experimental Mucormycosis
Authors: Gebremariam Teclegiorgis , Gu Yiyou , Singh Shakti , Kitt Therese , Ibrahim Ashraf S
Published: January 2021

Background

Mucormycosis is a life-threatening infection that predominantly occurs in immunocompromised hosts. Liposomal amphotericin B (L-AMB) and isavuconazole (ISAV) are commonly used antifungal drugs to treat mucormycosis. However, the efficacy of combination therapy of L-AMB + ISAV compared to monotherapy is unknown. We used an immunosuppressed mouse model of pulmonary mucormycosis to compare the efficacy of L-AMB + ISAV vs. either drug alone.

Methods

ICR mice were immunosuppressed with cyclophosphamide (200 mg/kg) and cortisone acetate (500 mg/kg) on Days -2, +3, and +8 relative to intratracheal infection with 2.5 x 105 cells of Rhizopus delemar 99-880, or 2.5 x 106 cells of Mucor circinelloides. Treatment with L-AMB (10 mg/kg, given intravenously qd), ISAV (56 mg/kg, by oral gavage TID), or a combination of both started 8 h post-infection and continued through day +4. Placebo mice received vehicle control. Survival studies through day +21 and tissue fungal burden (by conidial equivalent [CE] using qPCR) on Day +4, served as primary and secondary endpoints.

Results

For mice (n=20) infected with R. delemar, L-AMB and ISAV equally prolonged median survival time and enhanced survival vs. placebo (19 and 16 days for L-AMB and ISAV, respectively, and overall survival of 50% for either drug alone, vs. 9 days and 5% overall survival for placebo, P< 0.002 for either drug vs. placebo by Log Rank test). Importantly, combination treatment enhanced median survival time (>21 days) and resulted in an overall survival of 80% (P< 0.05 vs. all treatments). Both antifungal drugs reduced tissue fungal burden of mice (n=10) lungs and brain by ~1.0-2.0 log vs. placebo-treated mice (P< 0.02 by Wilcoxon Rank Sum). Consistent with the survival data, treatment with combination therapy resulted in 2.0-3.5 log reduction in fungal burden of either organ vs. placebo and 1.0 log reduction vs. either drug alone (P< 0.005). Similar results were obtained using mice infected with M. circinelloides.

Conclusion

L-AMB + ISAV demonstrate greater activity vs. monotherapy treatment in immunosuppressed mice infected with either of two common causes of mucormycosis. These studies warrant further investigation of LAmB + ISAV combination therapy as an optimal therapy of human mucormycosis.

Disclosures

Therese Kitt, MD, Astellas Pharma (Employee) Ashraf S. Ibrahim, PhD, Astellas Pharma (Research Grant or Support)
753. Performance Characteristics of Diagnostic Assays in Blastomycosis
Authors: O’Dowd Timothy , McHugh Jack , Wengenack Nancy , Theel Elitza , Vergidis Paschalis
Published: January 2021

Background

Blastomycosis has historically been a difficult diagnosis to establish, often initially misdiagnosed as bacterial pneumonia. Serologic assays and polymerase chain reaction (PCR) tests are available, but their performance is not well defined. The objective of this study was to characterize their performance.

Methods

Subjects were identified via chart review of patients diagnosed with blastomycosis from 2005 to 2020. A definitive diagnosis was based on fungal culture, histopathology, or cytology. Performance characteristics of the Blastomyces antibody enzyme linked immunosorbent assay (ELISA), immunodiffusion (ID), complement fixation (CF), urine and serum antigen ELISAs, and PCR were evaluated in patients with confirmed blastomycosis. Data on patient demographics, location of disease, and mortality was also collected.

Results

We identified 193 patients with blastomycosis. The mean age was 51.8 years (range, 11-84) and 73.6% of patients were male. 42.5% resided in Minnesota, 18.1% in Wisconsin, and 12.9% in Iowa. Diagnosis was based on culture in 142 (73.2%) or histopathology/cytology in 67 (34.7%) patients. Granulomatous inflammation was present in 73.1% (38/52) while 21.2% (41/193) had evidence of extrapulmonary dissemination.

The antibody, ID, and CF assays were positive in 43.5% (37/85), 35.1% (33/94) and 20.5% (8/39) of patients, respectively. Sensitivity of Blastomyces PCR was 40% (4/10) in sputum and 75% (21/28) in bronchoalveolar lavage (BAL) fluid. Blastomyces urine and serum antigen tests were positive in 68% (34/50) and 50% (9/18) of cases, respectively, while the urine antigen was positive in 63.6% (7/11) of disseminated cases. Patients had a positive Histoplasma urine antigen test in 54.1% (20/37) and Aspergillus galactomannan in BAL in 34.8% (8/23) of cases. Serum beta-D-glucan test was positive in 16.7% (2/12). 90-day mortality was 21/193 (10.9%) and median time from diagnosis to death was 18 days.

Conclusion

In this cohort, Blastomyces urine antigen was the most sensitive noninvasive test, with similar performance in pulmonary and disseminated disease. However, its utility is limited by poor specificity due to cross-reactivity. Blastomyces PCR from BAL fluid demonstrated the highest sensitivity. Blastomyces antibody, ID, and CF had poor sensitivity.

Disclosures

All Authors: No reported disclosures
758. Epidemiology of Tick-Borne Encephalitis (TBE): A Traveler′s Perspective
Authors: Pugh Sarah , Erber Wilhelm , Pilz Andreas , Schmitt Heinz-Josef
Published: January 2021

Background

Tick-borne Encephalitis (TBE) is a CNS infection caused by the TBE virus (TBEV), transmitted by ticks or by ingestions of unpasteurized dairy products. Persisting sequelae occur in up to 50% of patients and case fatality rates are 0.4-6% (up to 20% in Russia). There is no specific treatment, but prevention exists. New areas of TBEV circulation were recently identified. Here the current distribution of the TBEV by the end of 2019 is summarized.

Methods

Data were obtained from solicitation of local expert data from countries in Europe and Asia on TBEV isolation, type of surveillance/reporting, past/current case counts, and vaccine uptake, supplemented by literature searches. Countries were classified as suggested by the European Centers for Disease Prevention and Control (ECDC) as TBE- “predisposed” (competent ticks present), “imperiled” (TBEV isolated), “affected” (sporadic autochthonous cases) or “endemic” (annually autochthonous cases).

Results

TBE has now been diagnosed in Eurasia from the United Kingdom, Norway and France in the west, northern Italy in the south, central/eastern Europe, Russia, China on to Japan in the east. “New endemic” countries in the last five years include the United Kingdom, the Netherlands, as well as “new endemic regions”, e.g. in France, Norway, Germany, Finland and Poland. Six countries are considered as predisposed only, three as imperiled, five as affected and 29 as endemic. Misclassification is likely as some countries have no testing (no test), incomplete testing and/or underreporting.

Conclusion

The main considerations of TBEV risk for oversea travelers to Eurasia are: 1) the exact region and terrain within a country; 2) the planned type of (outdoor) activity; 3) the reliability of within country TBEV surveillance. TBE incidences per region may fluctuate log-fold over just a few years and low reported case counts may reflect a lack of testing, and/or preventive measures including vaccine uptake, and underreporting. As the incidence of TBE is unpredictable, prevention measures should be considered for any person traveling or residing in a recognized TBE “risk area”.

Disclosures

Sarah Pugh, PhD, Pfizer (Employee, Shareholder) Wilhelm Erber, PhD, Pfizer (Employee, Shareholder) Andreas Pilz, PhD, Pfizer (Employee, Shareholder) Heinz-Josef Schmitt, MD, Pfizer (Employee, Shareholder)
760. A Silent Threat: Seroprevalence of Chagas Disease in Latin Americans Living in Long Island, New York
Authors: Michelen Yamil E , Milla Lucia , Sin Eric , Taub Erin , Saldivar Miguel A , Marcos Luis
Published: January 2021

Background

Chagas Disease (CD), a neglected tropical disease of Latin America (LA) is caused by the parasite Trypanosoma cruzi, transmitted by the triatomine insect (kissing bug), and known to cause cardiomyopathy (CMP), megacolon or achalasia. Despite the population of Latin Americans, by birth or descent, in Long Island (LI), New York (NY) approximating 20%, information regarding prevalence of CD in this region is scarce. This study aims to determine the seroprevalence and risk factors for T. cruzi infection among hispanics in LI.

Methods

This is a cross-sectional study. Inclusion criteria included, birth or living in LA for > 3 years, mother born or lived in LA for ≥3 years, and residency in Suffolk County, LI. Patients were screened by Chagas Detect™ Plus Rapid Test (immunochromatographic strip assay for the qualitative detection of human IgG antibodies to T. cruzi; InBios Rapid test). Seropositivity was confirmed by enzyme immune assay and immunoblot. Participants answered a questionnaire regarding demographics and risk factors of CD.

Results

A total of 121 subjects (55.4% male) were tested from February 2018 to February 2020. Twelve were seropositive confirmed cases (9.9%; 66.7% male), with 9 cases from El Salvador (75%, p=0.06). Factors associated with infection were living in a palm house (OR=14.1, CI 2.7-74.7), history of triatomine bite (OR=9.5 CI=1.75–51.7), living in a house with triatomine (OR= 9.02, CI=1.9 – 42.8), and having relatives diagnosed with Chagas (OR= 7.6, CI=1.4 – 39.2). T. cruzi infected were most likely to have donated blood (OR=9.4, 95% CI=2.3–3.6). Two cases (16.6%) had CMP and did not qualify for treatment. One had gastrointestinal disease (8.3%). Eight started treatment with benznidazole.

Conclusion

In conclusion, we found a prevalence of 9.9% of T. cruzi infection in this high-risk population of LI. Two cases were diagnosed with CMP during this screening study highlighting that there are unrecognized cases of CD in this region where 20% are Hispanics. Such high prevalence and unrecognized disease, highlights the importance of raising awareness among providers of early screening and to prevent potential deadly outcomes.

Disclosures

All Authors: No reported disclosures
761. Antimicrobial Resistance Trends at a Pediatric Hospital in Guatemala City, 2005-2019
Authors: Graff Kelly E , Windsor W Jon , Calvimontes Mirella , Toledo Mario Augusto Melgar , Rivera Jose , Santos Lucy , Dominguez Samuel , Asturias Edwin J , Mata Maria Remei Gordillo
Published: January 2021

Background

Antimicrobial resistance (AMR) is an increasing global threat to public health, particularly in Latin America. Most published data are based on adults with limited pediatric reports regarding resistance trends. Our study evaluated AMR rates in a large tertiary pediatric hospital in Guatemala City and the association with clinical outcomes.

Methods

We analyzed AMR rates for six bacterial species (Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus) identified from blood cultures from the WHONET database between 2005-2019. Resistance was determined using CLSI cut-offs on the VITEK and Sensititre systems. Student’s t tests and simple linear regression models were performed. A retrospective review was performed on 99 pediatric patient charts with positive blood cultures (June 2018-May 2019) to assess clinical outcomes.

Results

Klebsiella and Acinetobacter were the most prevalent organisms throughout the 15 years of surveillance, with 2019 sensitivities demonstrating carbapenem-resistance in 99 (57%) and 57 (91%) of isolates, respectively. Increased resistance rates were noted for all Gram-negative organisms evaluated, with particular clinical and statistical significance noted for K. pneumoniae with imipenem (4.3% average resistance increase per year (PARPY), p-value < 0.0001), ciprofloxacin (4.5 PARPY, < 0.0001), and piperacillin-tazobactam (3.4 PARPY, < 0.0001), as well as A. baumannii with imipenem (2.9 PARPY, p-value < 0.0001), cefepime (1.7 PARPY, < 0.0001), and ciprofloxacin (2.5 PARPY, 0.0002). In contrast, resistance rates decreased for S. aureus with oxacillin (-2.7 PARPY, 0.0015). A mortality rate of 20% among our 99-patient cohort was detected. Of the 37% who received optimal therapy, the median time to optimal therapy was 90 hours.

Acinetobacter baumannii resistance to imipenem, 2005-2019

Klebsiella pneumoniae resistance to imipenem, 2005-2019

Staphylococcus aureus resistance to oxacillin, 2005-2019

Conclusion

Significant rises in AMR among pediatric patients in a large tertiary hospital in Guatemala City have occurred over 15 years. This likely contributed to delays in optimal antimicrobial therapy, increased exposure to broad spectrum antibiotics, and potentially increased mortality. Improved antimicrobial stewardship, infection prevention, and rapid diagnostic testing are needed in order to combat this growing problem.

Disclosures

Kelly E. Graff, MD, BioFire Diagnostics, LLC (Grant/Research Support) Samuel Dominguez, MD, PhD, BioFire (Consultant, Research Grant or Support)
764. Correlates of Lost to Follow-up Among Newly Diagnosed Older People with HIV in Ukraine
Authors: Allen Amy J , Zeziulin Oleksandr , Postnov Oleksandr , Rozanova Julia , Litz Taylor , Zaviryukha Irina , Kiriazova Tetiana , Shenoi Sheela
Published: January 2021

Background

Ukraine has the second largest HIV epidemic in Eastern Europe and Central Asia. Older People with HIV (OPWH) are at increased risk of poor outcomes compared to younger patients. We examined the prevalence and correlates of loss to follow-up (LTFU) among newly diagnosed patients in Ukraine.

Methods

Retrospective chart review was conducted of 400 patients newly diagnosed with HIV July 1, 2017 - Dec 1, 2018. Data was collected from clinics in the city of Odessa and surrounding regions. OPWH were ≥50 years old at diagnosis and LTFU was defined as no contact with the HIV clinic for 90 days. Demographic, clinical characteristics, and follow-up outcomes were examined, and multivariate logistic regression was used to estimate the adjusted odds ratios at 95% confidence intervals.

Results

Of the 400 people living with HIV, median age was 50 (IQR35-55), 196 (49%) were women, and 177 (44%) had CD4< 200cell/mm3 at diagnosis. Overall, 65 (16.5%) were LTFU from diagnosis and 54/65 (83%) were lost after their first appointment at the HIV clinic. Among those lost to follow-up, 49 (75%) were ≥50 at the time of diagnosis. Multivariate analysis showed LTFU was associated with age >50years (aOR 3.6, CI 1.8-7.3, p=0.001), lack of ART prescription (aOR 16.4, CI 8.5-31.8, p= 0.001), and living outside the city of Odessa (aOR 2.9, CI 1.5-5.7, p=0.002). Figure 1 shows the breakdown of lost to follow-up for OPWH.

Figure 1. Retainment in HIV Care for OPWH compared to those <50 years old.

Conclusion

LTFU among OPWH is significantly greater than younger people with HIV, and associated with lack of ART and living in nonurban settings. OPWH may benefit from differentiated HIV service delivery to reduce loss to follow up and interventions tailored to improving HIV outcomes for OPWH in resource-limited settings are urgently needed.

Disclosures

All Authors: No reported disclosures
765. Epidemiological And Clinical Features Of Rickettsiosis
Authors: Hammami Fatma , Koubaa Makram , Chakroun Amal , Rekik Khaoula , Smaoui Fatma , Elleuch Emna , Marrakchi Chakib , Jemaa Mounir Ben
Published: January 2021

Background

Rickettsiosis is a common tick-borne disease in tropical regions. The treatment is usually delivered in front of high index of suspicion, since the diagnosis confirmation might be delayed. We aimed to study the epidemiological and clinical features of rickettsiosis in our region.

Methods

We conducted a retrospective study including all patients hospitalized in the infectious diseases and pediatric department for confirmed rickettsiosis between 1995 and 2017. The diagnosis was confirmed by serological tests (seroconversion) or a positive polymerase chain reaction assays for Rickettsia.

Results

There were 424 patients among whom 232 (54.7%) were male. The mean age was 39 ±18 years. There were 62 children aged ≤18 years (14.6%). During six months period, from May to October, 360 patients were diagnosed with the disease (84.9%). In total, 334 patients had a close contact with animals (78.7%). The revealing symptoms were fever (100%), arthralgia (77.6%), cephalalgia (72.4%) and vomiting (44.8%). Physical examination showed maculopapular skin rash in 350 cases (82.5%), inoculation eschar in 105 cases (24.8%) and meningeal syndrome in 43 cases (10.1%). There were 43 cases (10.1%) of meningitis, 6 cases of meningoencephalitis (1.4%) and 5 cases of myocarditis (1.2%). Laboratory investigations revealed liver cytolysis (60%) and thrombocytopenia (57.5%). Doxycycline was used in 288 cases (68%), fluoroquinolones in 113 cases (26.6%) and macrolide in 23 cases (5.4%). The mean duration of antibiotics was 8 ±4 days. The disease evolution was favourable in 418 cases (98.6%). Four patients (1%) were dead and 2 patients (0.4%) were transferred to intensive care unit.

Conclusion

Rickettsiosis is not a rare disease. Careful clinical and laboratory investigations guide the diagnosis process, which is confirmed with serological tests.

Disclosures

All Authors: No reported disclosures
767. Identification and Management of Diarrhea in Children Under Five in Bamako, Mali
Authors: Cuttin Karen , Dupont Elizabeth , Keita Adama Mamby , Sow Samba , Kotloff Karen
Published: January 2021

Background

Diarrhea is a leading cause of death for Children Under Five Years Old (CUFYO) worldwide, and Mali has the second highest diarrhea-related case fatality rate among African countries. The World Health Organization’s Integrated Management for Childhood Illness (IMCI) handbook provides recommendations for management of acute watery diarrhea (AWD), including: increased fluids, continued feeding, and zinc supplementation. It restricts antibiotics to dysentery. The 2018 Malian Demographic and Health Survey noted low rates of rehydration and zinc use. This study aimed to evaluate how provider knowledge, beliefs, and practices (KBPs) align with IMCI recommendations for diagnosis and management of diarrhea in Mali.

Methods

This qualitative cross-sectional study interviewed 136 providers who manage diarrhea in CUFYO in Bamako, Mali from July - August 2017. Providers included: doctors (D), pharmacists (P), market vendors of allopathic medications (MV), traditional healers (TH), and vendors of traditional medicines (TV). Participants were randomly selected and presented with scenarios depicting diarrheal syndromes. They provided a diagnosis, etiology of illness, and management recommendations. Providers were surveyed on KBPs regarding IMCI recommendations.

Results

Only 43% of providers provided the IMCI definition of AWD. Participant-IMCI concordant diagnosis varied by provider group for AWD (D-73%, P-67%, MV-31%, TH-18%, TV-40%), Dysentery (D-38%, P-75%, MV-38%, TH-61%, TV-40%), and Some Dehydration (D-31%, P-4%, MV-4%, TH-7%, TV-40%). Only 41% of all providers identified dehydration as a sequela of AWD; 18% noted mortality. Etiologies of AWD cited included: infection, teething, diet, hygiene, and many others. Participants volunteered treatment of AWD with fluids (D-52%, P-8%, MV-0%, TH-0%, TV-0%), but not zinc (0%). MK alone offered inappropriate use of antibiotics for AWD (23%).

Conclusion

Provider identification and management of diarrheal syndromes in CUFYO remain largely inconsistent with IMCI recommendations across all sectors of providers interviewed, specifically for rehydration therapy and zinc supplementation.

Disclosures

All Authors: No reported disclosures
769. Mortality Among Inpatients After the Initiation of ‘Treat All’ With Dolutegravir in Botswana
Authors: Klinger Amanda E , Kronen Ryan J , Barak Tomer , Mophuthegi Patricia , Makhema Joseph , Zash Rebecca , Shapiro Roger
Published: January 2021

Background

Botswana was the first African country to implement a ‘treat all’ dolutegravir (DTG)-based treatment program for all adults. We studied whether this transition made a short-term impact on inpatient mortality among people living with HIV (PLWHIV).

Methods

From Dec 2015-Nov 2017, data were collected prospectively on all patients admitted to the medical wards of a district hospital in Botswana. Tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) was the first-line recommended antiretroviral treatment (ART) regimen for all ART-naïve adults with CD4 < 350 until May 2016, when it was replaced by TDF/FTC/DTG without CD4 restriction (‘treat all’). Multivariable logistic regression was used to compare mortality by ART regimen.

Results

Of 1,969 patients admitted, 41.5% were PLWHIV and of these 62.9% were on ART prior to admission. Before ‘treat all’, 160 (58.0%) of 276 PLWHIV were on ART prior to admission, and post-implementation 354 (65.4%) of 541 PLWHIV were on ART prior to admission (p=0.01). Among 315 patients on EFV-based ART and 85 on DTG-based ART prior to admission, demographics were similar (Table 1), except for more recent ART initiation with DTG, and lower median CD4 cell count with DTG (256 vs. 339 cells/mm3). Tuberculosis (TB) and community acquired pneumonia were the leading causes of hospitalization for both regimens. Death occurred in 178 (21.8%) PLWHIV, including 29% not on ART and 19% on any ART (p=0.003). Overall, 38% who initiated ART < 3 months prior to admission died (23.7% DTG, 48.8% EFV), and 36% with CD4 cell count < 50 cells/mm3 died (42.9% DTG, 30.8% EFV). Fewer deaths occurred among those on EFV (18%) compared with those on DTG (27%). However, controlling for CD4 count and timing of ART start, the risk of mortality among those on DTG and EFV was similar (aRR 1.08, 95% CI 0.62, 1.87). TB was the leading cause of death (40.1% off ART, 31.8% on DTG, 22.2% on EFV).

Table 1. Demographics, clinical characteristics, and outcomes of people living with HIV (PLWHIV) admitted to Scottish Livingstone Hospital, stratified by ART regimen prior to admission.

Conclusion

We found no improvement in inpatient mortality among PLWHIV during the shift to ‘treat all’ with DTG-based ART in Botswana. Decreasing high inpatient HIV mortality will require increased testing in the community to detect and treat PLWHIV prior to disease progression, and improved screening for opportunistic infections.

Disclosures

All Authors: No reported disclosures
770. Otherwise Unavailable Non-Malarial Parasitic Disease Treatment Drugs in the United States: an Update from CDC Parasitic Diseases Drug Service
Authors: Chancey Rebecca J , Yu Yon , Yu Patricia , Jolly Julian , Montgomery Susan
Published: January 2021

Background

The Centers for Disease Control and Prevention’s (CDC) support to clinicians includes providing access to certain drugs exclusively available through CDC for diseases that lack, or have limited market availability of, FDA-approved therapeutics in the U.S. These drugs are provided by CDC under expanded access Investigational New Drug (IND) applications, authorized by the FDA, to treating physicians. The CDC Parasitic Diseases Drug Service provides treatment drugs for patients with parasitic diseases, including travelers, immigrants and refugees from endemic countries.

Methods

CDC’s records for patients for whom drug was released over a 10-year period were reviewed.

Results

From 2010–2019, the annual number of drug releases for patient treatment ranged from 21–113 (median 99). Benznidazole, a treatment for Chagas disease, was the most common drug released for patients between 2012–2018, ranging from 42–63% of total drug releases annually. Sodium stibogluconate (Pentostam® 1), for treatment of certain presentations of cutaneous, visceral, and mucocutaneous leishmaniasis, accounted for 6–22% of annual releases over the last 10 years. While requests for treatment for human African trypanosomiasis are rare, in 2019 CDC released eflornithine and nifurtimox for one patient who met criteria for treatment according to the 2019 WHO recommendations.2

Conclusion

Recent changes to release frequency of triclabendazole, benznidazole, nifurtimox, and sodium stibogluconate are likely due to FDA-approval and commercial availability of previously investigational drugs. Triclabendazole is now FDA approved for treatment of Fasciola infection in persons ≥6 years old and benznidazole is now FDA approved for treatment of Chagas disease in children 2–12 years old. Miltefosine has also been approved by FDA for treatment of certain leishmaniasis infections. CDC has successfully pursued expiry extensions of drugs with manufacturers, FDA, and other partners to ensure continued domestic availability of treatment options when there has been no or limited production of newer lots. CDC’s Parasitic Diseases Branch can be reached by telephone: 404-718-4745 or email: parasites@cdc.gov.

1 Pentostam® is made by GlaxoSmithKline

2 WHO interim guidelines for treatment of gambiense HAT. Geneva: 2019.

Disclosures

All Authors: No reported disclosures
773. Screening for Chagas disease in East Boston, Massachusetts from 2017 – 2020 reveals 0.9% prevalence
Authors: Manne-Goehler Jennifer , Davis Jillian , Perez Juan Huanuco , Salazar Jaime Gallegos , Gomes Jim , Salazar Alejandra , Camelo Ingrid , Collins Katie , Park Hong-Sun , Hochberg Natasha , Hamer Davidson , Barnett Elizabeth , Barnett Elizabeth , Koehler Julia
Published: January 2021

Background

This study reports on the results of a screening program for Chagas disease in East Boston.

Methods

Based at the East Boston Neighborhood Health Center, the Strong Hearts Program offers continuing medical education sessions on Chagas disease to providers in Adult Medicine, Pediatrics, Family Medicine and Obstetrics. Providers are encouraged to offer one-time screening for Chagas disease for all patients who lived in Mexico, South or Central America for ≥6 months, at their discretion. A commercial lab performs the initial screening test using the Hemagen ELISA while confirmatory testing is performed at the US CDC. For each patient, completion of screening requires a multi-step process consisting of splitting the serum sample to save a frozen aliquot for send out to CDC if the ELISA is positive/indeterminate, monitoring screening results to send the saved aliquot to the CDC if indicated, filling out the CDC requisition, shipping the serum aliquot, and monitoring the result returning from the CDC. Patients diagnosed with confirmed Chagas disease are referred to Boston Medical Center for further evaluation and treatment if indicated.

Results

From 3/21/2017 – 5/18/2020, 8,142 patients were screened. 423 (5.2%) patients had an initial positive test, 7,669 (94.2%) initially tested negative and 50 were indeterminate (0.6%). Among those with a positive screening result, 76 were confirmed to have T. cruzi infection for an overall prevalence of 0.93% in this population. 293 (69.3%) patients with positive screening tests had a negative (discordant) confirmatory test, 18 (4.3%) had an indeterminate test, and 36 (8.5%) had results that were unavailable or pending as of this analysis. None of the indeterminate screening tests were positive upon confirmation.

Conclusion

Prevalence of infection with T. cruzi was nearly 1% among patients in East Boston who had lived in Latin America. Diagnosis of Chagas was challenging due to a large number of false positive screening tests. The resource burden imposed by current screening options is itself a barrier to addressing Chagas disease. Given the significant prevalence of Chagas disease in the US, increased access to tests (i.e., two-step screening conducted through commercial laboratories) and screening assays with improved specificity are needed.

Disclosures

All Authors: No reported disclosures
774. Sexual Behaviors and Attitudes of Intimate Partners of Ebola Survivors
Authors: Cunningham Hannah M , Wohl David , Tozay Sam , Reeves Edwina , Pewu Korto , Johnson Harrieta , Williams Gerald , Conneh Tonia , DeMarco Jean , Fischer William , Brown Jerry
Published: January 2021

Background

Sexual transmission of the Ebola virus (EBOV) from male survivors to their partners has been well-documented. While studies have characterized the sexual behaviors of male survivors of Ebola Virus Disease (EVD), there is little focus on their intimate partners. This study seeks to describe the attitudes and sexual behaviors of women who have had condomless sex with male survivors of the 2014-16 Ebola outbreak in Liberia, West Africa.

Methods

Participants were recruited through voluntary referral by their sexual partners, all of whom were participants in a longitudinal EVD survivor cohort. From February to March 2020, 30 women (age range: 19-53 years) were enrolled and surveyed regarding their sexual behaviors with a focus on perceptions of risk for acquisition of Ebola from their partners and the measures taken to address this risk. Mix method quantitative and qualitative assessment of survey responses was completed. Content analysis was used to consider open-ended questionnaire responses.

Results

Few women reported full compliance with the 2016 World Health Organization (WHO) recommendations for safer sex with EVD survivor partners, but 50% described utilization of a safer se x strategy to reduce risk of transmission. Major themes identified include: (1) an inaccurate perception of no or low risk of sexual transmission of Ebola virus, (2) negative attitudes towards condoms, (3) a preference for abstinence among those seeking to avoid infection, and (4) positive attitudes towards health care worker advice.

Conclusions

Future outbreaks will benefit from intervention programs to address knowledge gaps among women and their male survivor partner regarding the risk of sexual transmission of Ebola and clear communication about effective strategies to reduce this risk.

Disclosures

All Authors: No reported disclosures
775. The Burden of Arboviral Infection in the Military Health System, 2011-2019
Authors: Wellington Trevor , Fraser Jamie , Hickey Patrick , Lindholm David
Published: January 2021

Background

Travel-related arboviral infections are important preventable, emerging infectious diseases, with an estimated annual global toll of US$950 million. We investigated the burden of arboviral infections in the military health system (MHS).

Methods

KAPOS (Deployment and Travel Health: Knowledge, Attitudes, Practices, and Outcomes Study) is a multi-cohort study evaluating the burden of travel-associated diseases in the MHS. The MHS Data Repository was searched for International Classification of Diseases (ICD)-9/10 codes for arboviral infection in military beneficiaries receiving care in military treatment facilities (direct care) or civilian centers (purchased care) for fiscal years 2011-2019. Diagnostic codes were classified as Dengue, Chikungunya, Zika, or other arboviral infection. 755 outpatient charts in the direct-care system were randomly selected for diagnostic validation using Armed Forces Health Surveillance Center case definitions, and review of travel history, medical comorbidities, and pre-travel counseling.

Results

11,066 unique-patient ICD codes for arboviral infections were identified; 6356 (57.4%) were direct care; 4710 (42.6%) were purchased care; 889 (8.0%) were inpatient. Median age was 31 years; 5110 (46.2%) were active duty. The most frequent ICD codes for arboviral infection were Japanese encephalitis virus (JEV) (n=4483), dengue (DENV) (n=1786), yellow fever (YF) (n=230), Zika virus (ZIKV) (n=217), West Nile virus (WNV) (n=171), and chikungunya virus (CHIKV) (n=91). DENV codes were confirmed in 166/249 (66.7%) charts; CHIKV in 23/41 (56.1%), and ZIKV in 15/129 (11.6%). No cases of JEV were confirmed in 171 encounters; all codes referred to JEV vaccine administration. 173/204 (84.8%) of confirmed arboviral cases did not undergo pre-travel counseling.

Conclusion

Arboviral infections constitute a substantial burden of preventable infections within the MHS. Dengue contributed the largest burden of arboviral infection when corrected for accuracy. Coding for ZIKV and JEV likely overestimated the burden of these diseases in the MHS. Low rates of pre-travel counseling among patients with confirmed, non-endemic arboviral infections represent an opportunity for increased emphasis on travel counseling and insect-avoidance precautions.

Disclosures

All Authors: No reported disclosures