bluuebunny/crossref_metadata_2025 huggingface dataset:
348. Kidney Function Decline Among HIV-infected Thai Adults: Is Low Vitamin D One of the Factors?
Authors: Hlaing Than Win , Putcharoen Opass , Avihingsanon Anchalee , Kerr Stephen
Published: October 2019

Background

The prevalence of both hypovitaminosis D and Chronic Kidney disease (CKD) are high among Thai HIV-infected adults. Therefore, we examined the association of hypovitaminosis D and kidney function decline among HIV-infected Thai adults.

Methods

Using data prospectively collected from the HIV-NAT long-term cohort, we selected patients who were on ART, and virologically suppressed for ≥6 months. Baseline was defined as when the patient had a serum 25 OHD measured, with estimated Glomerular filtration rate (eGFR) above 60 mL/minute. Participants with eGFR measured at least twice a year were analyzed in the study. The primary outcome was kidney function impairment assessed as eGFR decline. Generalised estimating equations (GEE) were used to assess associations between the outcome and patient comorbidities and disease-related characteristics, including age, sex, body mass index (BMI) hypertension, gout, diabetes mellitus, co-infections with Hepatitis B or C viruses HIV-viral load and co-variate interactions with vitamin D status defined as normal, insufficient or deficient.

Results

A total of 435 participants were observed longitudinally through observations over the median follow-up of 24 (IOR 12–48) months. The median age of the participants was 46.6 (IOR 38.06–54.29) years. Median serum 25 OHD was 23.4 (IQR 18.5–29) ng/mL, and 209 (48%) and 126(29%) had insufficient and deficient 25 OH levels, respectively. Median baseline eGFR was 95 (IQR 82.70–104.93) mL/minute/l.73 m2. We found a significant interaction between BMI and vitamin D concentration (P = 0.02). In our multivariate model, the adjusted mean predictions of eGFR change at 24 months for patients with BMI ≥25 kg/m2 and deficient, insufficient and sufficient vitamin D were 89.8 (88.3–91.4), 91.2 (90.1–92.4) and 92.8 (91.3–94.4), respectively. In those with BMI <25 kg/m2 and deficient, insufficient and sufficient Vitamin D the adjusted mean predictions in eGFR change were 92.0 (91.1–93.0), 91.6 (90.9–92.3) and 92.3 (91.3–93.3), respectively.

Conclusion

HIV-infected Thai adults with high BMI (25 and above) but who are vitamin D deficient had a statistically significant eGFR decline. Further studies in larger populations with multi-ethnic groups are warranted.

Disclosures

All authors: No reported disclosures.
364. Association of Maternal ARV Use with Microcephaly in HIV-Exposed Uninfected Children
Authors: Williams Paige L , Yildirim Cenk , Chadwick Ellen G , Van Dyke Russell B , Smith Renee , Correia Katharine , DiPerna Alexandria , Seage George R , Hazra Rohan , Crowell Claudia S
Published: October 2019

Background

Perinatal HIV transmission has dramatically decreased with combination antiretroviral (ARV) regimens, but complications among HIV-exposed uninfected (HEU) children, such as microcephaly, warrant ongoing surveillance.

Methods

We evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a prospective cohort study conducted by the PHACS network at 22 US sites. Microcephaly was defined using 2000 CDC Growth z-scores for head circumference (HC) measured at 6–36 months of age (z-score <−2) and using Nellhaus standards (<2nd percentile) after age 3 (“SMARTT” criteria), or using Nellhaus standards across all ages. Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero ARV exposure and microcephaly status, adjusted for potential confounders. Sensitivity analyses were conducted. Neurodevelopmental functioning was compared between HEU children with vs. without microcephaly.

Results

Among 3055 SMARTT participants enrolled as of April 2017 with a HC measurement over 5.1 years median follow-up (IQR = 3.0, 7.2), 159 (5.2%, 95% CI: 4.4–6.1%) had microcephaly identified by Nellhaus criteria and 70 (2.3%, 95% CI: 1.8–2.9%) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4.7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (aRR=2.02, 95% CI: 1.16, 3.51) and SMARTT criteria (adjusted RR = 2.56, 95% CI: 1.22, 5.37). These associations were more pronounced among children exposed to combination regimens of efavirenz which included zidovudine+lamivudine than those including tenofovir+emtricitabine (Figure 1). Associations of microcephaly with efavirenz persisted in several sensitivity analyses (Figure 2). Protective associations were observed for darunavir exposure (aRR = 0.50; 95% CI: 0.24, 1.00). HEU children with microcephaly had lower mean scores on neurodevelopmental assessments at ages 1 and 5 years and higher prevalence of impairment than those without microcephaly.

Conclusion

Efavirenz exposure during pregnancy was associated with a higher risk of microcephaly in infancy and childhood. These findings may support identification of alternatives to efavirenz as part of first-line ARV therapy.

Disclosures

All authors: No reported disclosures.
365. Neurocognitive Function Change after Switching from Efavirenz to Rilpivirine in HIV-Infected Adults: A Randomized Control Trial
Authors: Kaewpoowat Quanhathai , Thongton Wirongrong , Robertson Kevin , Chaiwarith Romanee , Robbins Nathaniel , Supparatpinyo Khuanchai
Published: October 2019

Background

HIV-associated neurocognitive disorders (HAND) remain problematic even in the antiretroviral therapy (ART) era. Efavirenz (EFV) is well known for neuropsychiatric side effects and has been associated with worsening neurocognitive performance (NC). We hypothesized that switching from an ART regimen with EFV to one with rilpivirine (RPV) would improve NC.

Methods

This single-center, open-label, superiority, randomized controlled trial was conducted at Maharaj Nakorn Chiang Mai Hospital June 2018 to March 2019. HIV- infected adults (≥18 years), virologically suppressed on an EFV-containing regimen for at least 12 months, who met Frascati’s criteria of asymptomatic neurocognitive impairment (ANI), were randomized to a switching arm (RPV-containing regimen) vs. a control arm (EFV-containing regimen). The primary objective was to compare the improvement of NC at month 6 (M6) after switching. Secondary outcomes were individual NC domains, tolerability, and safety after switching regimens.

Results

20 ANI participants (10 per group) completed the study. 11 participants showed NC improvement at M6: 6 in the switching arm and 5 in the control arm. Global neuro deficit scores (GDS), figure learning, and figure memory at M6 significantly improved in both arms (P < 0.05). Verbal memory and speed of information processing improved over time in the switching arm only (0.6 (0.1–1.0); P = 0.02, and 0.7 (0.1–1.2); P = 0.03, respectively). However, no significant differences between the two groups were observed. Male gender, age < 50 and initiation of ART within 5 years after diagnosis all trended toward an association with improved NC. No tolerability issues or clinical significant adverse events were reported.

Conclusion

Despite some positive trends, switching from an EFV-containing regimen did not significantly improve NC. This finding was consistent with previous reports. A larger study with longer follow-up may be warranted.

Disclosures

All authors: No reported disclosures.
371. Tuberculosis and HIV Co-infection at a Tertiary Care Hospital in Thailand
Authors: Nimitvilai Sireethorn , Jintanapramote Kavita
Published: October 2019

Background

TB is the most common opportunistic infections (OIs) among patients living with HIV and associated with morbidity and mortality. The objective of the study was to describe epidemiology and characteristics of TB in newly diagnosed HIV patients.

Methods

Retrospective study was conducted at Nakhonpathom hospital, a 722-bed tertiary care hospital in Thailand during October 2016 and September 2018. The data on demography and outcome were collected.

Results

There were 369 newly-HIV diagnosed patients. Of these, 182 patients (49.3%) presented with AIDS-defining illnesses. TB was the most common (80 patients), followed by PCP (49 patients), cryptococcal meningitis (13 patients) and invasive salmonellosis (6 patients). Medical records of 29 HIV-TB patients were incomplete and were excluded from the study. Out of 51 HIV-TB patients, the median age was 41 (range 18–63) years and 39 (76.5%) were male. The median CD4 counts was 62.5 (range 7–773) cells/µL. Twenty-six (51.0%) had only pulmonary TB, 13 (25.5%) had only extra-pulmonary TB, and 12 (23.5%) had disseminated TB. Among extra-pulmonary TB, TB lymphadenitis was seen in 13, followed by intraabdominal TB in 8, TB meningitis in 4, and TB pleura in 3 patients. The mortality rate of HIV-TB in our study was 11.8%.

Conclusion

TB is the most common OIs that occurs among patients with advanced HIV disease. The outcome was unfavorable, with death in 11.8%. Strategies to improve early diagnosis and treatment are warranted.

Disclosures

All authors: No reported disclosures.
378. Seroprevalence of Helicobacter pylori among HIV-Infected Patients in a Tertiary Care Hospital in Busan, South Korea
Authors: Eun Lee Jeong , Hee Lee Sun , Lee Shinwon , Kim Kye-Hyung , Ok Lee Soon
Published: October 2019

Background

As human immunodeficiency virus (HIV) management has become more successful during the past years, the importance of non-AIDS-defining cancer such as gastric cancer has increased. Gastric cancer is the second most common cancer, and the third leading cause of cancer-related deaths in South Korea. Chronic inflammation of the gastric mucosa with Helicobacter pylori (H. pylori) is associated with gastric cancer, the highest incidence of which is observed in South Korea. The objective of this study was to evaluate the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients.

Methods

In a hospital-based survey, HIV-infected patients attending Outpatient Department of Pusan National University Hospital were enrolled between October 2018 and January 2019. Socio-demographic information was evaluated using questionnaires, serological status of H. pylori infection was tested with commercial H. pylori serology kits (Helicobacter pylori IgG ELISA, IBL, Germany).

Results

A total of 302 patients were included in the study. Two hundred and Sixty-one patients (86.4%) were males and 41 (13.6%) were females. Their median age was 54 years (range, 23–81 years), median CD4+ count was 667 /μL (7–1,699 /μL). The overall seropositivity of H. pylori in HIV-infected patients was 30.1%. Age-specific seroprevalence was as follows: 20–29 years, 12.5%; 30–39 years, 15.6%; 40–49 years, 38.6%; 50–59 years, 36.2%; 60–69 years, 27.9%; and ≥70 years, 18.2%. A lower seroprevalence of H. pylori was observed among patients younger than 40 years; however, it was not significant (P = 0.063). The risk factors associated with H. pylori seropositivity were alcohol consumption [adjusted odds ratio (OR): 1.99, 95% confidence interval (CI): 1.17 to 3.39; P = 0.011] and CD4 cell count ≥350/μL (OR = 4.32; 95% CI 1.51–12.36; P = 0.006).

Conclusion

HIV-infected patients had a lower seroprevalence of H. pylori compared with general population (30.1% vs. 49.1%). Alcohol consumption and CD4 cell count ≥350/μL were significantly associated with H. pylori seropositivity.

Disclosures

All authors: No reported disclosures.
379. Clinical Management of HIV-associated Pneumocystis jirovecii Pneumonia in Rural Nigerian Communities: Public Health Interventions and Impact
Authors: Onokala Ozioma , Nwabueze Emmanuel , Ijezie Echey
Published: October 2019

Background

The prevalence of Pneumocystis jirovecii Pneumonia (PJP) is increasing among vulnerable Persons Living with HIV (PLWH) in rural communities. In such communities, optimum clinical management of PJP in PLWH, is often limited by sub-optimal coordination of healthcare programs and inadequate human resources. The study evaluated the impact of interventions implemented by public health programs, to improve the clinical management of PJP among PLWH in rural Nigerian communities.

Methods

The longitudinal study was done at 30 randomly selected rural communities in Nigeria. Program interventions included: decentralization of comprehensive Anti-Retroviral Therapy (ART) to primary healthcare facilities; and strategic private–public partnerships to ensure provision of free medications for ART and prophylaxis/treatment of PJP, (according to National Treatment Guidelines). Additional interventions included: training of indigenous healthcare workers on clinical management of PJP; task-shifting; routine monitoring and evaluation of PJP indicators to ensure program quality, among others. Real-time data from Patients’ Care Cards were utilized for pre- and post-intervention assessments in January 2014 and January 2019, respectively. Chi-square was applied as inferential statistics; P < 0.05 indicated statistical significance.

Results

The number of PLWH on ART, who received primary PJP prophylaxis with Trimethoprim-Sulfamethoxazole (TMP-SMX), increased from 2,280 (pre-intervention) to 14,461 (post-intervention). PLWH (55 females; 40 males), exhibited TMP-SMX intolerance and were offered Dapsone for primary PJP prophylaxis. PJP diagnosis and treatment for female PLWH increased from 5% (pre-intervention), to 82% (post-intervention). PJP diagnosis and treatment for male PLWH increased from 3% (pre-intervention), to 79% (post-intervention). Incidences of PJP increased with age, viral load, ART interruption, and late presentation to HIV care. Secondary PJP prophylaxis for PLWH (after the completion of pneumonia treatment) increased from 2% (pre-intervention) to 90% (post-intervention).

Conclusion

The interventions significantly improved the clinical management of PJP in PLWH. They are recommended for implementation by health programs in rural communities.

Disclosures

All authors: No reported disclosures.
380. Characterizing Host Factors, Treatment Strategy, and Clinical Outcomes of Group A Streptococcus Orthopedic Infections
Authors: Nadeem Naiha , Saraiya Nidhi , Nori Priya , Szymczak Wendy , Boland-Reardon Carmel
Published: October 2019

Background

The annual incidence of invasive β-hemolytic group A streptococcus (GAS) infections in the United States is approximately 3.8 cases per 100,000 patients with 10–30% mortality. But data in GAS orthopedic infections is limited. We sought to characterize patient factors, medical and surgical management, and clinical outcomes from GAS orthopedic infections at our medical center.

Methods

A total of 12 patients with GAS orthopedic infections (necrotizing fasciitis, osteomyelitis, prosthetic joint infection, septic arthritis, or tenosynovitis) from July 2017 and March 2019 were included. Medical records were reviewed for site of positive GAS culture (blood, wound, joint fluid, or tissue cultures), demographics, comorbidities, surgical management, and antibiotic regimen and duration. The primary outcome was cure at 90 days defined as clinical improvement without recurrent or new infection, or further surgical or medical management at 90 days after treatment completion. The secondary outcome was erythrocyte sedimentation rates (ESR) before and after treatment.

Results

The median age of the 12 patients was 56 years (range 3–75); 58% were female and 58% had a body mass index ≥30 kg/m2. The median Charlson comorbidity index score was 3 (range 0–7) with 58% having diabetes mellitus. Two patients had either rheumatoid arthritis or monoclonal gammopathy (Table 1). Most patients had severe infections; 33% with necrotizing fasciitis and 25% with orthopedic implants. All patients had an elevated initial ESR, including 75% with ESR >40 mm/h. 92% required surgery, including 42% amputations and 17% prosthesis removals. Patients were mostly treated with β-lactams and vancomycin (92%); only 50% received clindamycin or linezolid. Most patients (75%) required at least 2 weeks of antibiotics. Five patients (42%) were not cured at 90 days, and 1 died of infectious complications (Table 2).

Conclusion

Severe GAS orthopedic infections necessitate both surgical management and prolonged antibiotics. 42% of our patients were not cured at 90 days and most eventually required amputation. Toxin mediators, clindamycin and linezolid, were underutilized. Chronic suppressive antibiotics should be considered for patients with orthopedic implants, especially those with durable immune suppression.

Disclosures

All authors: No reported disclosures.
388. Spinal Implant Infections Treated with Debridement and Hardware Retention
Authors: Rivero Cynthia , Martinez Santiago , Pardo Orlando , Jahan Cintia , Fuego Segundo , Ignacio Dapas juan , Vila Andrea
Published: October 2019

Background

Surgical site infections following spinal surgery affect 0. 3 to 20% of patients. The longer the infection, the greater the chance of antibiotic treatment failure due to the establishment of mature microbial biofilm on the hardware, requiring its removal for infection eradication.

Methods

Retrospective cohort of patients with microbiologically confirmed SII following spinal surgery treated with debridement and retention. SII was defined as the presence of clinical signs of deep surgical site infection with 2 or more positive culture results of tissue surrounding the implant taken during surgical debridement; or from CT guided biopsy. Inclusion criteria: adults with a 1º episode of microbiological confirmed SII diagnosed from 2008 to 2017 with >2 years of follow-up, treated with implant retention. Definitions Early-onset infection (EOI): infection < 1 month following implant placement. Late onset infection (LOI): between 30 days and 1 year after implant placement. Delayed onset infection (DOI): >1 year of implant placement. Statistical analysis made in Graph Pad Prism 5. 0.

Results

We analyzed 19 patients with SII treated with hardware retention. Mean age was 54 (21–70) years, 63% were female. Comorbidities, clinical manifestations and motive for surgery are in Table 1 and Figure 1. Hardware material used was titanium 15(79%) and steel 4(21%). In addition to the hardware,11 patients (57. 9%) underwent bone grafting, 4 experienced treatment failure (4/11 = 36. 4%); 2 patients had nonmetallic material inserted (carbon polymer), the 2 patients experienced failure. 16 patients (84. 2%) had EOI, 2 (10. 5%) LOI, 1 (5. 3%) DOI. Failure requiring implant removal was observed in 26. 3% (n = 5), 2 of the cases were EOI, 2 LOI and 1 DOI. Bacterial characteristics of patients are shown in Table 2. 47,4% of patients required more than one debridement (Figure 2). In the lineal regression model, treatment failure was associated with bone grafting (P = 0. 04) and the use of carbon polymer materials (P = 0. 007).

Conclusion

Treatment of SII with debridement plus antimicrobials treatment is acceptable, with a rate failure of 26%. In LOI and DOI spinal implant retention is more prone to fail. Bone grafting and the presence of polymers seem to be associated with treatment failure of conservative strategies.

Disclosures

All authors: No reported disclosures.
408. Single-cell Sequencing Identifies Variability in Host Response Among Different Genera of Influenza Viruses
Authors: Thielen Beth Kristine , Christensen Jaime , K. Strain Anna , Shen Steven , Langlois Ryan
Published: October 2019

Background

Seroprevalence and surveillance studies indicate that influenza C virus (ICV) infection is common among humans, and initial exposure occurs early in life. ICV often causes milder disease than influenza A and B viruses, but the mechanisms underlying differences in pathogenicity remain poorly understood.

Methods

To compare early events of infection in natural target sites, we cultured primary human tracheal/bronchial epithelial cells under air-liquid interface conditions to allow differentiation. We-infected these cells with human strains of influenza A, B or C virus. Cells were infected at low MOI (0.1) to ensure populations of directly infected cells and uninfected neighboring cells. To compare the early immune response and cell tropism among these viruses, we performed single-cell RNA sequencing of mock- and influenza-infected cells. In parallel, we infected cells pretreated with interferon to mimic later rounds of infection after an early immune response is initiated.

Results

Infection of primary cells by all three viruses was confirmed by RT-qPCR of bulk cell lysates. As expected, prior exposure to interferon β results resulted in reduced levels of viral transcripts. At the single-cell level, we identified expression of genes associated with specific cell types, including basal, ciliated and secretory cells. We also identified expression of interferon stimulated genes, but these genes were not homogeneously expressed among all cell subpopulations and varied among cultures infected with different influenza viruses. We also found different patterns in gene expression in cells previously exposed to interferon, suggesting that host environment varies over subsequent rounds of infection.

Conclusion

Single-cell sequencing is an important tool for studying the host response to influenza infection in complex cellular environments such as the respiratory tract, in which cells vary in their susceptibility to infection and antiviral response. Further analysis will characterize differences among directly infected vs. neighboring cells and correlate responses with pathogenicity.

Disclosures

All authors: No reported disclosures.
415. Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants
Authors: Caserta Mary T , Wang Lu , Chu Chin-Yi , Slaunwhite Christopher , Holden-Wiltse Jeanne , Corbett Anthony , Falsey Ann R , Topham David , Mariani Thomas , Walsh Edward E , Qiu Xing
Published: October 2019

Background

RSV infection is common in infants with a majority of those affected displaying mild clinical symptoms. However, a substantial number develop severe symptoms requiring hospitalization. We currently lack sensitive and specific predictors to identify a majority of those who develop severe disease.

Methods

High throughput RNA sequencing (RNAseq) of nasal epithelial cells defined airway gene expression patterns in RSV-infected subjects. Using multivariate linear regression analysis with AIC-based model selection, we built a sparse linear predictor of RSV disease severity, the Nasal Gene Severity Score-NGSS1. Using a similar statistical approach, we built an alternate predictor based upon genes displaying stable expression over time (NGSS2). We evaluated predictive performance of both models using leave-one-out cross-validation analyses.

Results

We defined comprehensive airway gene expression profiles from 106 full-tem previously healthy RSV-infected subjects with a range of RSV disease severity prospectively enrolled in the AsPIRES study. Nasal samples were obtained during acute infection (day 1–10 of illness; 106 samples), and convalescence (day 14–28 of illness; 69 samples). All subjects had a primary infection and were assigned a cumulative clinical illness severity score (GRSS) (Table 1). From the RNA seq data 41 genes were identified as the NGSS1 which is strongly correlated with disease severity (GRSS) in both the naive (ρ=0.935) and cross-validated analysis (ρ of 0.813). As a binary classifier (mild vs. severe), NGSS1 correctly classifies 89.6% of the subjects following cross-validation (Figure 1). Next, we evaluated genes that were stably expressed in both acute illness and convalescence samples in 54 subjects with data from both time points. Repeating the regression based step wise model selection identified 13 genes as NGSS2, which was significantly correlated with GRSS (ρ = 0.741). This model has slightly less, but comparable, prediction accuracy with a cross-validated correlation of 0.741 and cross-validated classification accuracy of 84.0% (Figure 2).

Conclusion

Airway gene expression patterns, obtained following a minimally-invasive nasal procedure, have potential utility as prognostic biomarkers for severe infant RSV infections.

Disclosures

All authors: No reported disclosures.
419. Initial Evaluation of Engagement and Utilization of the National Sexually Transmitted Diseases Curriculum
Authors: Newman Gretchen Snoeyenbos , Unruh Kenton T , Karpenko Andrew Y , Bauer Karin M , Johnston Christine , Workowski Kimberly , Spach David H
Published: October 2019

Background

The National Sexually Transmitted Diseases Curriculum (NSTDC) is an online, guideline-based, interactive curriculum developed at the University of Washington in Seattle with funding from the Centers for Disease Control and Prevention (CDC) National Network of STD Clinical Prevention Training Centers (NNPTC). The NSTDC has dual-functionality to provide users with the option of engaging in (1) sequential, longitudinal learning and/or (2) quick access to specific content. We describe the first evaluation of the reach, utilization and effectiveness of the NSTDC.

Methods

We evaluated user data collected from survey completion, Google Analytics, and the Health Professional Application for Training (HPAT) between the launch of NSTDC in February 1, 2017 through August 31, 2018. Chi-square and ANOVA tests were used to determine significant differences between prescribers, nurses, and non-clinicians.

Results

month period and 54,910 hours of CE awarded. Registered users were mostly women (16,133, 84%), and 8,476 (44%) were registered nurses, with an additional 6,052 (34%) prescribing providers (physicians, nurse practitioners, physician assistants, and dentists). The most common programmatic focus was primary care (4,886, 25%). While 18,175 (95%) of users were in the United States, users were located around the world (Figure 1). Referral patterns differed significantly by occupation (Figure 2). Users engaged deeply with the curriculum. Average site session time was 28 minutes for registered users and 14 minutes for all users. Registered users completed an average of 4.37 out of 7 total modules. Nurses were more likely to complete all modules, (48% vs. 34% of prescribers and 30% of non-clinicians, P < 0.0001). Over 15,000 users answered at least one optional check-on-learning (COL) question. On average, 77% of COL questions were answered in modules where COL questions were initiated. Over 60% of the users found the content and experience highly satisfying. Overall 39% of users intended to change practice following completion of the modules.

Conclusion

The NSTDC has a broad reach, leads to high user engagement and satisfaction, and fosters intent to change practice. This web-based curriculum is a novel and effective strategy to disseminate recommendations from CDC Guidelines.

Disclosures

All authors: No reported disclosures.
424. Use of the ResistancePlus® MG Multiplex PCR Assay to Determine the Prevalence of Mycoplasma genitalium and Macrolide Resistance in a High-Risk US Population
Authors: Cartwright Charles , Harris Ayla , Levandoski Michael , Pherson Amanda , Nye Melinda
Published: October 2019

Background

Mycoplasma genitalium is a significant agent of sexually transmitted infection (STI). Cure rates have declined as rates of macrolide resistance has become increasingly prevalent. Diagnosis of M. genitalium infection and macrolide resistance detection is possible using nucleic-acid amplification tests (NAAT); use of such assays could improve patient management and antimicrobial stewardship. In this study we used one such assay, ResistancePlus MG (RPMG) to determine the prevalence of M. genitalium infection and macrolide resistance in a cohort of patients attending 3 public sexual health clinics in mid-Atlantic US states.

Methods

De-identified urogenital samples submitted to the LabCorp facility in Burlington, NC for routine Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) NAAT testing from 3 public sexual health clinics were analyzed in the study. All samples had been collected in the Aptima Specimen Collection system and tested with the Aptima Combo 2 CT/NG NAAT. A total of 1,261 samples (770 male, 491 female) from this cohort were successfully tested for M. genitalium and macrolide-resistance mediating mutations (MRMM) using the RPMG multiplexed PCR assay.

Results

The prevalence of M. genitalium in this patient cohort was 10.4% (131/1,261), not significantly different to the prevalence of C. trachomatis (12.0%; P = 0.202) but significantly higher than the prevalence of Neisseria gonorrhoeae (6.7%; P = 0.0009). Sixty of the 131 M. genitalium positives were also positive for MRMM and thus azithromycin resistant.

Conclusion

M. genitalium infections were common amongst unselected individuals evaluated for treatable STI in the eastern United States and the rate of macrolide resistance in this population was significant. In addition, the RPMG assay was shown to be a simple and accurate method for simultaneously diagnosing M. genitalium infections and detecting MRMM and could be used to inform therapeutic decisions.

Disclosures

All authors: No reported disclosures.
431. Asymptomatic Latent Syphilis and Stroke in Geriatric Patients; Analysis of Routine Syphilis Tests
Authors: Tago Sayaka , Ishiguri Tomohiro , Hirai Yuji
Published: October 2019

Background

Increasing incidence of syphilis in the young to middle age population is a concern in Japan. Although stroke is a known complication of syphilis, it is unknown for asymptomatic latent syphilis (ALS). Our aim was to investigate the results of routine syphilis tests to find the association between stroke and ALS in geriatric patients.

Methods

This retrospective observational study included patients above 65 years of age who underwent the rapid plasma reagin (RPR) and treponema pallidum hemagglutination assay (TPHA) tests (Showa Medical Science, Kanagawa, Japan) as routine evaluation at an institute from August 2014 to February 2019. Asymptomatic patients with positive TPHA were diagnosed with ALS. Clinical data were collected, including the age, gender, history of stroke, underlying diseases, complications (thoracic aortic aneurysm, aortic regurgitation, dementia), habits, indication for syphilis test, and syphilis description in the medical records. Negative TPHA was the exclusion criterion. A multivariate analysis was used to determine the independent risk factors for stroke. All variables with P < 0.1 in the univariate analysis were evaluated using the multivariate model with the level of significance set at P < 0.05. Statistical analyses were performed using R version 3. 3. 1.

Results

A total of 10,117 geriatric patients underwent the syphilis test in the study period. The TPHA test was positive for 96 patients (0.95%), including 45 (46.9%) men, who were included in the study. The median age was 86 years (range: 65–102). The RPR test was positive for 51 cases (53.1%). The indications for syphilis test were syphilis screening for admission (n = 71), endoscopy (n = 16), health checkup (n = 3), and others (n = 6). No past treatment history for syphilis was found in the medical records. Syphilis descriptions were found for 6 patients (6.25%). One patient had been treated for ALS. A multivariate analysis revealed that positive RPR [odds ratio: 3.39; 95% confidence interval: 1.17 to 9.78; P = 0.0241] was associated with history of stroke.

Conclusion

For ALS in geriatric patients, positive RPR is associated with history of stroke. Medial evaluation about risk for stroke is necessary for ALS in geriatric patients.

Disclosures

All authors: No reported disclosures.
434. Concurrent Gonococcal Infections with Differing Susceptibility Results from the Enhanced Gonococcal Isolate Surveillance Project (eGISP)
Authors: St. Cyr Sancta , Quilter Laura , Pham Cau D , Torrone Elizabeth , Weinstock Hillard
Published: October 2019

Background

Concurrent gonococcal infections could impact treatment success in cases of anatomic site-specific strains with different antimicrobial susceptibilities; however, little is known about same-patient differences in susceptibility as most antibiotic resistance surveillance is based on only male urethral isolates.

Methods

In August 2017, the enhanced Gonococcal Isolate Surveillance Project (eGISP) began collecting male and female genital and extragenital gonococcal isolates from patients in 12 STD clinics. Minimum Inhibitory Concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, gentamicin, cefixime, ceftriaxone and azithromycin were determined by agar dilution. We identified patients with isolates from multiple anatomic sites of infection collected during the same clinic visit. Isolate sets were categorized as pairs or triplets based on the number of culture positive anatomic sites. We identified same-patient isolate sets with differing MICs (≥2 dilution difference) for each antibiotic, and identified if the difference affected susceptibility categorization. All isolates in a set were tested in the same batch run by the same laboratory.

Results

From August 2017-February 2019, 280 isolates were collected from 135 patients, representing 136 isolate sets (128 pairs and 8 triplets); one patient contributed 2 isolate sets. Of the 136 isolate sets, the majority (72; 53%) were grouped as genital and pharyngeal isolates (Table 1). Overall, 33 isolate sets (24%) had differing MICs for ≥1 antibiotic and 21 sets (15%) for ≥2 antibiotics. Across all anatomical site combinations, differing MICs were most common for ciprofloxacin (10.3%), penicillin (9.6%) and azithromycin (9.6%). Only 18 isolate sets (13%) demonstrated differing MICs where an isolate was considered susceptible and another was considered resistant or reduced-susceptible.

Conclusion

Among persons with concurrent gonococcal infections, MICs can vary by ≥2 dilutions between sites and may change susceptibility interpretation. Variation by the anatomic site can result from initial infection with multiple strains or differential development of resistance after infection. Continued surveillance of multi-site infections could help understand resistance development and inform patient management.

Disclosures

All authors: No reported disclosures.
444. Better Efficiency, Same Accuracy: Point-of-Care PCR for the Detection of Group A streptococcus in Noninvasive Skin Infections
Authors: Galdun Patrick D , Close Ryan M , Sutcliffe Catherine , Parker Dennie R , Reid Angelina , McAuley James , Hammitt Laura
Published: October 2019

Background

Group A streptococcus (GAS) is a common cause of skin and soft-tissue infections (SSTIs). Current diagnostic techniques are culture-based and time intensive, requiring the prescription of empiric antibiotics before results are available. New detection tools are needed to hasten the diagnosis and appropriate treatment of SSTIs. The Cobas® Liat® System is a point of care (POC), real-time PCR system developed by Roche Molecular Diagnostics and is used in the United States and Europe to detect GAS from throat swabs within 15 minutes. We evaluated the feasibility and performance characteristics of POC for the detection of GAS in non-severe SSTIs.

Methods

Wound swabs collected from patients presenting to the Whiteriver Indian Health Service Hospital with non-severe SSTIs requiring only outpatient treatment were eligible for inclusion. Two swabs were collected: one swab was cultured on sheep’s blood agar, and the other swab was tested using POC. Compared with culture, we determined the sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for POC to detect GAS in wound samples. We performed chart reviews 30-days from eligibility to assess the potential impact of POC systems on antibiotic use and healthcare utilization for SSTIs.

Results

To date, we have tested 100 (25%) of our target 400 samples (enrollment will be complete in August 2019). Of the 100 samples, 50 (50%) tested positive for GAS by POC, all of which were culture positive for GAS, 49 tested negative by POC (2 after a first invalid result), all of which tested culture negative for GAS (table), and 1 had an invalid POC result even after repeat testing (culture positive for MRSA only) and was excluded from further analysis. Among samples with a valid POC result, POC SN was 100%, SP was 100%, PPV was 100%, and NPV was 100%. The most common mono-infections were MRSA (22%), GAS (18%), and CoNS (6%). Among GAS cases, MSSA (32%) and MRSA (18%) co-infection was common.

Conclusion

POC PCR is highly sensitive and specific for the detection of GAS in non-severe SSTIs. To our knowledge, this is the first prospective study to use this technology for wound samples. POC PCR methods have the potential to accelerate identification of SSTI pathogens and improve antibiotic prescribing.

Disclosures

All authors: No reported disclosures.
462. Prospective Surveillance of Invasive Group A Streptococcal Infections in Toronto, Ontario, Canada: 1992–2017
Authors: Kandel Christopher , Daneman Nick , Demczuk Walter , Gold Wayne , Green Karen , Martin Irene , Plevneshi Agron , Powis Jeff , Rudnick Wallis , Sarabia Alicia , Schwartz Benjamin , Simor Andrew , Tyrrell Greg , Valiquette Louis , McGeer Allison
Published: October 2019

Background. Background

Invasive Group A streptococcal (iGAS) infections remain a substantial source of morbidity and mortality. We explore the clinical and molecular epidemiology of iGAS infections in Toronto, Ontario, Canada over a 26-year period.

Methods

The Toronto Invasive Bacterial Diseases Network has performed population-based surveillance for iGAS infections in metropolitan Toronto and Peel regions since 1992. Participating microbiology laboratories report and submit sterile site specimens for central processing. M typing was performed on iGAS isolates until September 2006; thereafter emm typing was performed. Clinical information was collected by chart review using standardized collection forms.

Results

Over the 26-year period there were 2819 iGAS infections, representing an average incidence of 2.85 per 100,000 residents with a nadir of 1.65 in 1993 and a peak of 4.52 in 2014. Nosocomial infections occurred in 8.9% (251/2,819). There was substantial variation in annual incidence rates over the study period with increases from 1992 until 2002 and then 2004 until 2014 (analysis for trend, P < 0.001). Skin and soft-tissue infections were the most common clinical presentation, accounting for 33.2% (936/2,819), followed by bacteremia without a focus in 15.4% (435/2,819). Necrotizing fasciitis was observed in 7.4% (208/2,819) and criteria for toxic shock syndrome were met in 17.6% (497/2,819). Overall case fatality within 30 days of hospitalization was 15.3% (95% confidence interval 14.0 to 16.6) and did not change over time. M serotype distribution varied yearly with the most common type being M1 at 22.2% (626/2,189) followed by M12 at 8.2% (230/2,189), then M89 at 5.8% (163/2,189). Antibiotic susceptibility was available from 1998 onwards with overall clindamycin susceptibility at 92.3% (1,957/2,121) and erythromycin susceptibility at 87.9% (1864/2,121).

Conclusion

The incidence of iGAS in Toronto, Ontario has varied over time, with no recent increase apparent. Similar to worldwide observations, M1 serotype was the most commonly isolated; most common serotypes demonstrated cyclical variation. Case fatality rates have remained relatively constant making the development of a vaccine imperative.

Disclosures

All authors: No reported disclosures.
468. Epidemiologic Features of Invasive Methicillin-Resistant Staphylococcus aureus and Group A Streptococcus Infections among Adults Who Inject Drugs in the San Francisco Bay Area, 2008–2017
Authors: Nadle Joelle , Apostol Mirasol , Libby Tanya , Reingold Art
Published: October 2019

Background

Injection drug use has been associated with infection with invasive methicillin-resistant Staphylococcus aureus (iMRSA) and invasive group A Streptococcus (iGAS). In light of the ongoing opioid epidemic, we sought to describe the epidemiologic features of iGAS and iMRSA infections among persons who inject drugs (PWID) in the San Francisco Bay Area.

Methods

Active, population-based surveillance for iMRSA and iGAS was conducted in three California counties during 2008–2017. We defined a case as recovery of MRSA or GAS from a normally sterile site in a surveillance area resident ≥18 years of age. We collected demographic and clinical information and history of injection drug use (IDU) in the past 12 months. Trends in the incidence of infection were assessed using the Cochran-Armitage test for trend. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated comparing PWID and non-PWID.

Results

Of the 6,705 iMRSA and 1,691 iGAS cases identified during 2008–2017, 764 (11%) and 241 (14%), respectively, were among PWID. The proportion of iMRSA cases reporting IDU increased from 9.6% in 2008 to 12.9% (P = 0.017) in 2017 (Figure 1); no significant trend was observed for iGAS cases (Figure 2). Among iMRSA and iGAS cases, PWID cases were younger than non-PWID cases (iMRSA median 46 vs. 63 years, P < 0.0001; iGAS 41 vs. 57 years, P < 0.0001) and were more likely to be homeless (iMRSA OR 8.3, CI 6.7–10.2; iGAS OR 5.4, CI 4.0–7.2), and diagnosed with endocarditis (iMRSA OR 5.9, CI 4.8–7.3; iGAS OR 2.8, CI 1.3–6.4) and internal abscesses (iMRSA OR 4.3, CI 3.5–5.3; iGAS OR 3.4, CI 2.1–5.5) (Table 1). For iMRSA, PWID cases were more likely than non-PWID cases to be community-associated, (OR 2.5, CI 2.1–2.9) and diagnosed with septic arthritis (OR 2.4, CI 1.9–3.0).

Conclusion

The proportion of iMRSA cases reporting IDU significantly increased between 2008 and 2017, in the San Francisco Bay Area. iMRSA and iGAS cases among PWID are younger, more likely to be homeless, and diagnosed with endocarditis and internal abscesses. Prevention measures targeting this younger population who are experiencing homelessness and/or are injecting drugs, may limit severe manifestations of iMRSA and iGAS. These prevention measures should include support of safe injection practices.

Disclosures

All authors: No reported disclosures.
513. Transmission of Carbapenem-Resistant Enterobacteriaceae in a Community-Based, Residential Care Setting: Nevada, 2018
Authors: Gomes Danica , Bardossy Ana , Gorzalski Andrew , Holmstadt Heather , Larson Sandra , Halpin Alison L , Chen Lei , Causey Kimisha , Njoku Chidinma V , Stone Nimalie D , Ogundimu Abimbola , Moulton-Meissner Heather , McAllister Gillian A , Gable Paige , Vlachos Nick , Walters Maroya S , Epstein Lauren , Forero Adrian
Published: October 2019

Background

Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) are often multidrug-resistant, and the KPC resistance determinant can be transmitted between bacteria. KPCOs are associated with healthcare facility exposures; identification in community-based, residential care settings is uncommon. In September 2018, the Washoe County Health District was notified of a KPC-producing Escherichia coli from a group home (GH) resident. We investigated the source of this KPCO and evaluated transmission in the GH.

Methods

A case was defined as detection of KPCO from a GH resident or staff from June 1 to November 30, 2018. Staff included caregivers who provided daily care (including toileting, bathing, feeding) and visiting healthcare workers. Residents and staff were offered KPCO screening to assess colonization status. Exposures were assessed by medical record review and interviews. Genetic relatedness of KPCOs was evaluated by whole-genome sequencing (WGS). Infection prevention and control (IPC) practices were reviewed.

Results

Overall, six cases were identified, including the index, two of seven staff screened and three of six residents screened. Three residents with KPCOs had recent hospitalizations and shared a bathroom in the GH; one overlapped on the same hospital unit as a patient with KPC-producing Klebsiella oxytoca. Staff with KPCOs were caregivers who had extensive contact with residents and their environment and no IPC training. Gaps in hand hygiene and environmental cleaning were observed. Organism was recovered from 4 positive screening tests as well as from blood cultures from the index case; all were KPC-producing E. coli. WGS showed that the five E. coli isolates were closely related, consistent with transmission, and harbored the same KPC variant as the K. oxytoca. No new cases occurred after IPC was improved.

Conclusion

A GH resident likely acquired KPCOs during a recent hospitalization, and extensive transmission among GH residents and staff occurred. Factors contributing to transmission included resident dependence on caregivers for daily care and minimal IPC knowledge among caregivers. Facilities with similar populations should increase IPC training to prevent transmission of resistant pathogens.

Disclosures

All authors: No reported disclosures.
545. Incidence of Carbapenem Non-Susceptible Acinetobacter spp. and Carbapenem-Resistant Pseudomonas aeruginosa Clinical Cultures among Patients in US Acute Care Hospitals, 2012–2017
Authors: Kazakova Sophia , Baggs James , Wolford Hannah , Olubajo Babatunde , Hatfield Kelly M , See Isaac , Bulens Sandra N , Reddy Sujan , Jernigan John A
Published: October 2019

Background

Carbapenem-nonsusceptible Acinetobacter spp. (CNAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are recognized causes of severe and difficult to treat healthcare-associated infections. This study estimated and compared the incidence of CNAB and CRPA among patients admitted to US acute care hospitals in 2012–2017.

Methods

We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of over 300 hospitals submitting data to the Premier Healthcare Database and Cerner Health Facts in 2012–2017. We included clinical cultures from any body site yielding Acinetobacter spp./P. aeruginosa non-susceptible/resistant to imipenem, meropenem, or doripenem. Cultures collected on days 1–3 of hospitalization were considered community-onset (CO) and cultures from later were hospital-onset (HO). Duplicate isolates identified within 14 days of an incident culture and surveillance cultures were excluded. For each year, a raking procedure generated weights to extrapolate the sample estimate to match the American Hospital Association distributions based on US census division, hospital bed capacity, teaching status, and urban designation. We compared estimated rates in 2017 vs. 2012 using weighted multivariable logistic regression adjusting for hospital characteristics and hospital-level clustering.

Results

In 2017, the estimated rates of HO and CO CNAB rates were 0.77 and 1.39/10,000 discharges, and HO and CO CRPA rates were 3.14 and 6.57, respectively. Compared with 2017, rates of HO CNAB decreased 49% (Odds Ratio (OR) 0.51; 95% CI: 0.34–0.75) and rates of CO CNAB decreased 29% (OR 0.71; 95% CI: 0.54–0.92). For CRPA, the incidence of HO decreased (OR 0.66; CI: 0.49–0.88) with no change in CO rates (OR 0.93; CI: 0.79–1.11). Assessment of cultures from sterile sites alone showed similar results, but they did not reach statistical significance, Figure 1.

Conclusion

We estimate significant national decreases in the rates of HO and CO CNAB, and HO CRPA. Risk factors and effective interventions to reduce CO CRPA might differ from CNAB and HO CRPA. Additional prevention strategies are needed to address CO CRPA.

Disclosures

All authors: No reported disclosures.