bluuebunny/crossref_metadata_2025 huggingface dataset:
309. Should Primary Care Practitioners Follow Hepatitis C Exposed Infants?
Authors: Merjaneh Nawal , Smotherman Carmen , Maraqa Nizar , Mirza Ayesha
Published: October 2019

Background

Hepatits C virus (HCV) infection in pregnancy is estimated between 1–4% and risk of vertical transmission ~5%. While the benefits of HCV testing for perinatally exposed infants under a year is debatable, a strategy for follow-up (F/U) is important. We instituted interventions to improve the F/U rate for HCV exposed infants in December 2012. Pediatric infectious diseases (PID) service was consulted in the newborn period to establish care. Perinatal HCV exposure was added to the infant’s electronic record. Educational brochures were given to guardians at discharge. We aimed to assess the efficacy of the interventions in improving the F/U rate.

Methods

A retrospective chart review of 227 HCV exposed infants born between January 2013 and December 2016 was done after obtaining IRB. Infant charts were reviewed for maternal age, race, insurance, HCV risk factors, HIV and Hep B co-infection, third trimester HCV PCR, delivery type, gestational age, birth weight and infant custody. Based on 2002 NIH guidelines: first visit at 6–8 weeks, second at 6–8 months, final visit ≥18 months of age. Maternal HCV infection is positive HCV antibody (Ab) during pregnancy, medical care defined as at least one infant PID clinic visit, and appropriate F/U as an 18-month visit for HCV (Ab) check. Univariate analysis is used for demographics, descriptive summaries were recorded as frequencies and percentages.

Results

214 infants included in analysis (1 deceased and 12 adopted and left area). Baseline characteristics of those who had medical care vs. not were similar except for infant custody and HIV co-infection 94/214 (44%) had medical care. Of those, 32/94(34%) had appropriate F/U while 62/94(66%) did not 31/214 infants were followed by primary care practitioners (PCPs) at our institution. Of those 24/31(77.5%) were either tested inappropriately or lost to F/U HIV co- infection and custody by a relative (not mom) increase the likelihood of F/U (P 0.003 and 0.002, respectively) 5 infants contracted HCV infection. One infant who lost to F/U was diagnosed incidentally in the ER.

Conclusion

Appropriate F/U for HCV exposed infants poses challenges despite established systems of care. Because current guidelines recommend antibody testing at 18 months, educating PCPs who are more likely to establish regular F/U is important for appropriate testing.

Disclosures

All authors: No reported disclosures.
318. Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) in Hispanic/Latinx and Black Participants: Efficacy, Bone and Renal Safety Results from a Pooled Analysis of 7 Clinical Trials
Authors: DeJesus Edwin , Federico Andrade Villanueva Jaime , Ramon Arribas Lopez Jose , Brinson Cynthia , Crofoot Gordon , Daar Eric S , Koenig Ellen , Podzamczer Daniel , Ramgopal Moti , Santana Jorge , Santiago Lizette , Tebas Pablo , Zorrilla Carmen , Guo Susan , Liu Ya-Pei , Zhong Lijie , Brainard Diana M , Carter Christoph C , Temme Lauren , Das Moupali
Published: October 2019

Background

People of color are underrepresented in clinical trials. TAF has shown improved renal and bone safety vs. TDF. We pooled 7 studies to evaluate efficacy/safety of TAF vs. TDF for ART initiation/switch in Hispanic/Latinx and Black participants.

Methods

Data from Hispanic/Latinx and Black adults who initiated/switched to TAF or TDF in 7 randomized trials (2 treatment-naïve, 5 suppressed switch) were analyzed. TAF-based regimens (elvitegravir/cobicistat/emtricitabine [FTC]/TAF, rilpivirine/FTC/TAF, FTC/TAF, or bictegravir/FTC/TAF) were compared with TDF-based regimens. Virologic suppression (VS; HIV-1 RNA < 50 c/mL, FDA snapshot) and % change in bone mineral density (BMD) and renal tubular biomarkers urine β-2-microglobulin (B2M):creatinine (Cr) ratio and retinol binding protein (RBP):Cr ratio are reported at W96.

Results

The pooled population (N = 5,825) included 1138 Hispanic/Latinx and 1324 Black participants. Treatment-naïve participants (n = 1,733) were 15% female, 25% Black, 19% Hispanic/Latino, with median age 34 years, HIV-1 RNA 4.6 log10 c/mL, CD4 405 cells/mm3. Switch participants (n = 4,092) were 13% female, 22% Black, 20% Hispanic/Latino, median age 45 years, CD4 653 cells/mm3. There was no difference in VS rate with TAF vs. TDF in any group. VS rate (TAF vs. TDF) in naïve participants: 88% vs. 84% (Hispanic/Latinx); 78 vs. 79% (Black); 87% vs. 85% (overall). VS (TAF vs. TDF) was well maintained in switch participants: 91% both arms (Hispanic/Latinx); 86% vs. 87% (Black); 90% vs. 88% (overall). TAF and TDF were well tolerated with few discontinuations due to adverse events (0.6–2%) in all groups. At W96 there was less impact on renal biomarkers in all groups initiating TAF (P < 0.001; table), and decreases in BMD were smaller (P < 0.005; table) vs. TDF. All groups switching from TDF to TAF experienced decreases in tubular proteinuria and improvements in BMD (both P < 0.001; table) at W96.

Conclusion

Hispanic/Latinx and Black participants who initiated/switched to TAF had significantly improved bone and renal parameters vs. TDF, with similar VS rates at W96. Efficacy and biomarkers were similar to the overall study population. These data in >2,400 Hispanic/Latinx and Black PLH demonstrate noninferior efficacy and safety advantages with TAF vs. TDF.

Disclosures

All authors: No reported disclosures.
321. Low Volumetric Bone Density at Proximal Femur in HIV-Infected Men and Its Risk Factors: Comparison with Community-Dwelling Non-Infected Men
Authors: Ho Kim Jung , Hong Namki , Ji Lee Woon , Seong Hye , young Ahn Jin , Jin Jeong Su , su Ku Nam , Chang Kim Hyeon , Yeom Joon-Sup , Rhee Yumie , yong Choi Jun
Published: October 2019

Background

Individuals with HIV infection is at increased risk of low area bone mineral density (BMD) and fracture. However, data regarding volumetric BMD (vBMD) of central bone determined by quantitative computed tomography (QCT) which can distinguish the cortical and trabecular bone component are limited.

Methods

From November 2017 to October 2018, we measured spine and hip vBMD in HIV-infected men aged 30 years or older at the tertiary center. QCT data were compared with 1:2 matched control by age- and body mass index (BMI) sampled from a community-based healthy individual cohort. HIV-specific risk factors for low total hip vBMD as a primary outcome were identified using multivariate linear regression models.

Results

A total of 83 HIV-infected men and 166 control were analyzed (mean age 47.4 vs. 47.0 year; BMI 23.3 vs. 23.7 kg/m2; P > 0.05). In HIV-infected men, vBMD of trochanter, intertrochanter and total hip was significantly lower than that of non-infected men. (198 ± 31 vs. 213 ± 32; 339 ± 50 vs. 356 ± 47; 280 ± 41 vs. 296 ± 41 mg/cc; all P < 0.05) Association between HIV infection and lower total hip vBMD remained robust (Adjusted β -14.4; P = 0.013) after adjustment for age, diabetes, smoking, and vitamin D status. In HIV cohort, low CD4 T-cell count at initial diagnosis (< 200 vs. ≥200 cells/μL; Adjusted β = −6.7, P = 0.015) and use of protease inhibitor (vs. integrase inhibitor; Adjusted β = −29.9, P = 0.029) were negatively associated with total hip vBMD, after adjustment for age, BMI, and duration of HIV infection, whereas tenofovir disoproxil fumarate use was not. (Adjusted β −12.1, P = 0.280) In HIV-infected men with low tertile total hip vBMD, the levels of β-crosslaps (0.42 ± 0.23 vs. 0.30 ± 0.16 ng/mL; P = 0.012) and osteocalcin (22.10 ± 8.65 vs. 16.57 ± 6.04 ng/mL; P = 0.001) were higher than those with middle-upper tertile total hip vBMD.

Conclusion

HIV-infected men had lower hip vBMD compared with age- and BMI-matched non-infected men. Low baseline CD4 T-cell count and protease inhibitor use were independent risk factors for lower total hip vBMD. High born turnover was attributable to the negative effect on born health of HIV-infected men.

Disclosures

All authors: No reported disclosures.
327. Barriers to Positive Health Outcomes in the HIV-Infected Cancer Clinic Population
Authors: Goldstein Alexa , Riedel David J
Published: October 2019

Background

Significant disparities in morbidity and mortality from cancer in HIV-infected persons exist compared with those with cancer in the general population. This study sought to identify psychological, social and economic factors impacting or impeding cancer care in the HIV-infected population.

Methods

A voluntary, anonymous one-time questionnaire was completed by patients diagnosed with cancer who are HIV-infected and HIV-uninfected at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC). Andersen’s Behavioral Model of Health Services Use served as the theoretical framework for assessing psychological, social, and economic barriers to care. We used the chi-square test to evaluate the association between HIV status and barriers to accessing cancer care.

Results

A total of 25 HIV-infected and 100 HIV-uninfected cases were included. More HIV-infected patients with cancer experienced self-esteem and fear barriers to a greater degree than their HIV-uninfected counterparts (28% vs. 15% for self-esteem, and 40% vs. 21%). A significant proportion of HIV-infected individuals reported experiencing insufficient social support (32% vs. 10% in the HIV-uninfected population, P = 0.01). HIV-infected individuals reported that they did not feel looked down upon in the cancer clinic. They also described that their cancer and HIV diagnoses were delivered in a similar manner by the provider.

Conclusion

Given that HIV-infected persons are experiencing lower survival rates for most cancer subtypes when compared with their HIV-uninfected counterparts, there is a need to further investigate the feelings of fear, low self-esteem, and insufficient support reported in the HIV-infected sample. Cancer care may need to be tailored to reflect the differences in psychological barriers and enabling resources that continue to be disproportionately prevalent in HIV-infected patients.

Disclosures

All authors: No reported disclosures.
334. Weight Change Associated with Antiretroviral Therapy Switch to Integrase Strand Transfer Inhibitor-Based Regimens
Authors: Saber Saghar , Bernstein Andrew B , Sparks Andrew D , Siegel Marc O
Published: October 2019

Background

An association between switching antiretroviral therapy (ART) to integrase strand transfer inhibitor (INSTI)-based ART and weight gain has been previously reported. However, insufficient data exists on risk factors associated with such weight gain.

Methods

We reviewed charts of 119 virally-suppressed HIV-positive patients switched from nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based ART to INSTI-based ART and compared their weight change over 17 months to 56 virally-suppressed patients who were maintained on NNRTI-based regimens over the same period.We looked at variables associated with weight gain including age, weight, body mass index (BMI), gender, CD4 count, starting ART, and final INSTI-based ART.

Results

The 119 patients switched to INSTI-based ART gained an average of 6.9 lbs compared with an average 1 lbs weight gain in the 56 patients who were maintained on NNRTI-based ART (P = 0.002). There was also a statistically significant difference in the percentage % weight change between the two groups (4.2% vs. 0.7%, P < 0.001).There was an average 1.2 lbs weight loss in 92 of the 119 patients with weights recorded 17 months before switching ART, compared with an average 6.7 lbs weight gain after the switch (P < 0.001).There was no association between gender, CD4 count at the time of switch, starting ART, or final INSTI-based ART with weight gain. However, patients weighing < 150 lbs at the time of switch had a greater % weight gain than patients weighing >200 lbs (6.9% vs. 2.7%, P = 0.02) and a trend to greater % weight gain than those weighing ≥150 to ≤ 200 lbs (6.9% vs. 3.8%, P = 0.06). There was marginal statistical significance when comparing those with BMIs < 25 to those with BMIs ≥25 to ≤ 30 (8.2 vs. 6.5 lbs, P = 0.069) and those with BMIs >30 (8.2 vs. 5.0 lbs, P = 0.057). There was an inverse correlation between age and weight gain, indicating that less weight was gained when switching to INSTI-based ART as the age of the patient increased (ρ = -0.211, P = 0.021).

Conclusion

Our study showed a statistically significant weight gain in patients switched from NNRTI- or PI- to INSTI-based ART compared with patients maintained on NNRTI-based ART.Baseline variables associated with greater weight gain included weight <150 lbs, BMI <25 and younger age.

Disclosures

All authors: No reported disclosures.
356. HIV-HCV Coinfection: An Investigation of CD4 T-Cell Reconstitution after HCV Direct-Acting Antiviral Treatment
Authors: Michienzi Sarah M , Cai Jiaqi , Harris Cydnee , Kim Sean , Patel Nimish , Badowski Melissa E , Chan Juliana , Martin Michelle T , Schriever Christopher A
Published: October 2019

Background

Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) can adversely affect CD4 cell count. Among patients with HIV-HCV coinfection, treatment with HCV direct-acting antivirals (DAAs) may be an opportunity to restore/reconstitute CD4 count. The primary objective of this study was to determine whether DAA treatment results in improved CD4 cell counts in HIV-HCV coinfected patients.

Methods

A retrospective multicenter cohort study was performed among 4 sites between 11/1/2013–4/12/2018. Patients were included if they were age ≥18 years, infected with both HIV and HCV, and received all-oral DAA therapy. Trained reviewers extracted demographics, comorbidities, receipt of antiretroviral therapy (ART), DAA treatment regimen/duration and HIV/HCV-related lab values, which included CD4, HIV RNA, and HCV RNA. Labs were restricted to the closest values before/after DAA treatment. The primary endpoint was changed in pre-DAA/post-DAA CD4 count. Descriptive statistic and Wilcoxan Signed Rank were used.

Results

There were 88 patients included. Most (78.4%) identified as male. Mean ± standard deviation (SD) age was 57.1 ± 9.6 years. The proportion of patients with undetectable pretreatment HIV RNA was 78.4%. Among the 97.7% of patients on ART, regimens included the following classes of ART: integrase strand transfer inhibitor (75.6%), non-nucleoside reverse transcriptase inhibitors (23.3%) and protease inhibitors (19.8%). Of the 87 patients who completed DAA therapy and had post-DAA labs drawn, sustained virologic response (SVR) was achieved in 96.6%. The median (interquartile range, IQR) CD4 counts before/after DAA treatment did not significantly differ [515 (349–704) vs. 554 (374–693), P = 0.80]. In the subset of patients with pre-DAA CD4 counts < 350 cells/mm3 (n = 23), CD4 count significantly improved before/after DAA treatment [235 (202–311) vs. 309 (189–392), P = 0.01].

Conclusion

The use of DAA therapy in HIV-HCV co-infected patients resulted in a significant increase in CD4 count in patients with pre-DAA CD4 < 350 cells/mm3. This may represent a high priority population for DAA treatment.

Disclosures

All authors: No reported disclosures.
402. Clinical Characteristics and Outcome of Staphylococcus lugdunensis Prosthetic Joint Infections
Authors: Masood Komal , Duggan Joan , Redfern Roberta , Georgiadis Gregory , Suleyman Geehan
Published: October 2019

Background

Although Staphylococcus lugdunensis is a coagulase-negative staphylococcus, it shares similar characteristics with S. aureus and is increasingly recognized as the cause of serious infections, including prosthetic joint infections (PJIs). The aim of this study was to determine the clinical characteristics and outcome of S. lugdunensis PJIs.

Methods

This was a retrospective multicenter study conducted from January 2007 through December 2017 involving consecutive adult patients with S. lugdunensis PJIs in northwest Ohio. Clinical and microbiologic characteristics, treatment modalities and outcome were evaluated.

Results

A total of 695 patients were evaluated and 29 (4%) patients met inclusion criteria (Table 1). All patients were Caucasian and 52% were female with a median age 68.8. Comorbidities included Diabetes Mellitus (34%), CAD (41%), CHF (20%), COPD (20%) and cancer (14%). The most common clinical presentations were pain (28/29, 97%), decreased range of motion (27/29, 93%) and joint swelling (21/29, 72%). Two patients had concomitant bacteremia. Knee was the most commonly affected joint (69%), followed by hip (24%). All isolates, except one, were susceptible to oxacillin. Thirteen (45%) patients had a two-stage revision, nine (31%) debridement with/without revision, six (21%) no surgical intervention and one (3%) a 1-stage revision. The majority of patients (71%) received ≥4 weeks of antibiotics (abx). Two patients with no surgical intervention and one with debridement received no abx. Another was discharged to hospice without intervention. Relapse was observed in two (15%) patients who had a 2-stage revision, four (44%) who had debridement, 6 (100%) who had no surgical intervention or 1-stage revision. Overall, there was a statistically significant difference in cure rates in patients who underwent 2-stage revision compared with other treatment modalities (P = 0.003) regardless of abx treatment regimen, including prolonged IV abx therapy. However, IV abx were superior to oral (P = 0.009).

Conclusion

Appropriate management of S. lugdunensis PJIs includes both aggressive surgical management with a prolonged course of abx with excellent clinical responses. Relapse is high in patients treated without two-stage revision irrespective of route or duration of abx therapy.

Disclosures

All authors: No reported disclosures.
416. Improvement in Syphilis and HIV Screening Rates at a Community-Based Emergency Department in Columbus, Ohio: Six Month Post-Intervention Analysis
Authors: Buffomante Ashley , Goldstein Philip , Hussain Cory , Malvestutto Carlos , Bazan Jose A , Sobhanie Mohammad Mahdee , Pollak Brandon , Koletar Susan , Nandam Kushal , Petke Carol , Combs Julie , Dick Michael , Lindsey Sommer
Published: October 2019

Background

Sexually transmitted infections (STIs) disproportionally affect individuals living in underserved areas and Emergency Departments (ED) can play a major role in STI screening. Given the overlapping risk factors for STIs, patients screened for gonorrhea and chlamydia should also be screened for syphilis and HIV. Rates of syphilis/HIV screening in the ED are very low and barriers include lack of knowledge about the risk/prevalence, difficulty with results interpretation, and concerns about follow-up.

Methods

The main study objective was to improve rates of syphilis/HIV screening in a community-based ED in Columbus, OH. A team of clinical providers, case managers, and social workers was formed to address barriers to screening. Using root cause analysis and data feedback, a multistep intervention that included provider education along with expert review of syphilis/HIV results was implemented to ensure proper screening, treatment and rapid linkage to care. Syphilis/HIV screening rates in the ED were compared between two periods: 2012–2017 (pre-intervention) and November 2018–April 2019 (post-intervention).

Results

Between 2012 and 2017, there were 24,427 ED encounters where any STI test was ordered. There were 23,652 (97%) tests for chlamydia, 23,637 (97%) for gonorrhea, 254 (1%) for syphilis, and 466 (2%) for HIV. Twenty-four (0.1%) encounters had screening that included all four tests. Six months after starting the intervention, there were 1,590 encounters where any STI test was ordered. There were 1,444 (91%) tests for chlamydia, 1,446 (91%) for gonorrhea, 493 (31%) for syphilis and 591 (37%) for HIV. Four hundred thirty-eight (28%) of encounters had screening that included all four tests.

Conclusion

Collaborative and practical interventions aimed at improving syphilis/HIV testing have resulted in dramatic increases in syphilis, HIV, and comprehensive STI screening (31-, 19-, 280-fold, respectively) over a relatively short post-intervention period. Additional steps are planned with the goal to further increase screening rates and improve linkage to prevention and treatment programs.

Disclosures

All authors: No reported disclosures.
439. Iclaprim Use for Acute Bacterial Skin and Skin Structure Infection (ABSSSI) is Not Associated with Hyperkalemia: Phase 3 REVIVE Studies
Authors: Huang David B , Noviello Stephanie S , Lodise Thomas , McKinnell James , Dwyer Jamie P
Published: October 2019

Background

Trimethoprim inhibits sodium channels in the distal portion of the renal tubule, thereby impairing renal potassium excretion. Trimethoprim has been associated with a greater risk of hyperkalemia compared with other antibiotics (amoxicillin, nitrofurantoin, cefalexin, ciprofloxacin). An analysis of Phase 3 studies was conducted to determine whether iclaprim, under development for ABSSSI and also a selective bacterial dihydrofolate reductase inhibitor like trimethoprim, is associated with hyperkalemia, relative to vancomycin, an antibiotic not associated with hyperkalemia.

Methods

A post-hoc safety analysis was conducted on pooled results of two Phase 3, double-blind, randomized (1:1), active-controlled trials (REVIVE-1/-2) in patients with ABSSSI. These trials compared iclaprim 80 mg fixed doses with vancomycin 15 mg/kg; both administered intravenously every 12 hours for 5–14 days. Hyperkalemia was defined as serum potassium (K) ≥5.5 mmol/L, if normal at baseline, while on study drug. Hyperkalemia was compared between treatment groups and stratified subgroup comparisons were performed.

Results

Demographics and baseline disease characteristics were similar between the pooled iclaprim and vancomycin groups (table). Hyperkalemia occurred during treatment in 1.5% (9/592) and 2.5% (15/599) of patients treated with iclaprim and vancomycin, respectively. Of the patients with hyperkalemia, one patient in each treatment group had moderate to severe renal impairment (creatinine clearance [CrCl] 15–59 mL/minute). Among patients with moderate to severe renal impairment on any RAS, KSD or K supplements, hyperkalemia occurred in 1/16 and 0/16 patients in the iclaprim and vancomycin groups, respectively, and in 2/83 and 0/46 patients with mild to no renal impairment. No patients with hyperkalemia experienced adverse events of palpitations, chest pain, myalgia, muscular weakness or fatigue.

Conclusion

No differences in hyperkalemia were seen between the iclaprim and vancomycin groups in the Phase 3 REVIVE studies. In general, few cases of hyperkalemia occurred among patients with renal impairment treated with concomitant angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers treated with iclaprim.

Disclosures

All authors: No reported disclosures.
465. Comparative Efficacy of Double vs. Single Antibiotic Regimens for the Empiric Treatment of MRSA-Induced Acute Bacterial Skin and Skin Structure Infection
Authors: Alhifany Abdullah A , Bifari Nisrin , Alatawi Yasser , Ullah Malik Saad , Almangour Thamer
Published: October 2019

Background

The initial management of Acute bacterial skin and skin structure infection (ABSSSI) is burdensome. It requires empirical antibiotic therapy that covers both gram-positive and gram-negative bacteria. Vancomycin plus aztreonam are the most commonly used antibiotic combination, nonetheless, they have many limitations which limits their use. Hence, many new single agents with MRSA and gram-negative coverage, oral options, and/or good safety profile have been developed to be a potential alternative such as: ceftaroline, ceftobiprole, tigecycline and the recent FDA approved antibiotic (delafloxacin). In the absence of head-to-head trials comparing these agents, we decided to conduct a network meta-analysis for these therapeutic regimens.

Methods

A Bayesian network meta-analysis of randomized clinical trials identified in PubMed/Medline and Embase databases was conducted. We performed both fixed and random effect models for clinical cure as the primary outcome of interest. Additionally, rankograms were generated using the surface under the cumulative ranking curve (SUCRA) to obtain the treatment ranking probabilities in relation to their relative effect.

Results

We identified 10 eligible studies involving 4,914 patients. The indirect comparison demonstrated that delafloxacin showed no difference in terms of clinical cure compared with ceftaroline (OR, 0.82, 95% Cr.I 0.39–1.8), ceftobiprole (OR, 0.79, 95% Cr.I 0.32–1.9), SOC (OR, 1.2, 95% Cr.I 0.62–2.4) and tigecycline (OR, 1.0, 95% Cr.I 0.45–2.2) in the fixed effect analysis, nor in the random-effect analysis (OR, 0.8, 95% Cr.I 0.26–2.2; OR, 0.78, 95% Cr.I 0.2–3.0; OR, 1.2, 95% Cr.I 0.51–3.1; and OR, 0.96, 95% Cr.I 0.30–3.0), respectively. Furthermore, the ranking probabilities in the fixed-effect and random-effect analysis showed that ceftaroline was ranked the first in terms of clinical cure (SUCRA, 40.02%) followed by ceftobiprole (SUCRA, 22.80%), delafloxacin (SUCRA, 16.60%), SOC (SUCRA, 13.80%), and then tigecycline (SUCRA, 6.70%).

Conclusion

Ceftaroline, ceftbiprole, delafoxacin, SOC and tigecycline are similarly effective. However, delafloxacin provides better convenience. Further comparative studies regarding their safety are needed.

Disclosures

All authors: No reported disclosures.
483. Case–control Study Evaluating the Risk of Stenotrophomonas maltophilia Pneumonia in Patients with Previous Exposure to Meropenem
Authors: Saraiya Nidhi , Chacko Jasmine , Goriacko Pavel
Published: October 2019

Background

Stenotrophomonas maltophilia (SM) is a growing cause of opportunistic nosocomial infections with a mortality rate of 23–77%. Previous studies have identified the use of broad-spectrum antibiotics, specifically carbapenems, as a risk factor for SM infection, but these findings were limited to secondary endpoints. Meropenem’s overall broad-spectrum activity but limited SM activity may favor SM colonization and infection.

Methods

Adult patients admitted between January 2016 and July 2018 with available culture data were identified using data mining software. Cases were defined by a positive SM respiratory culture between days 2 and 60 of admission and receipt of antibiotic treatment. Controls were defined by a respiratory culture negative for SM during the same period. The primary endpoint was to evaluate the exposure to at least 48 hours of meropenem between cases and controls, with exposure defined as at least 48 hours of meropenem treatment with the last dose given within 15 days of respiratory culture. Secondary endpoints were to evaluate exposure to at least 7 days of meropenem or other antipseudomonal antibiotics.

Results

A total of 225 patients were included, 106 as cases and 119 as controls. Baseline demographics and age-adjusted Charlson comorbidity index score were similar between groups. Twenty-one cases (19.8%) and 5 controls (4.2%) were exposed to at least 48 hours of meropenem before developing SM pneumonia. The odds of meropenem exposure was 5 times greater in cases than controls (OR = 5.6, P < 0.001). After adjusting for a longer length of stay before culture collection as a potential confounding variable, meropenem use was still associated with SM pneumonia (adjusted OR = 4.6, 95% CI 1.7–14.7). Significant associations were also found with exposure to at least 7 days of meropenem (OR = 4.7, 95% CI 1.52–14.77, P = 0.004) or other antipseudomonal antibiotics (OR = 3.0, 95% CI 1.59–5.71, P < 0.001).

Conclusion

This is the first study to evaluate meropenem as a risk factor for developing SM pneumonia. Even as little as 48 hours of meropenem exposure increases the risk of developing SM pneumonia. As one of the few modifiable risk factors for SM infection, judicious use of meropenem may reduce the incidence of SM infection and associated mortality.

Disclosures

All authors: No reported disclosures.
492. High Prevalence of Colonization with Carbapenem-Resistant Enterobacteriaceae Among Patients Admitted to Vietnamese Hospitals: Risk Factors and Burden of Disease
Authors: Tran Dien M , Larsson Mattias , Olson Linus , TB Hoang Ngoc , Kien Ngai Le , TK Khu Dung , Nguyen Hung D , Vu Tam V , Trinh Tinh H , Le Thinh Q , TT Phan Phuong , Nguyen Binh G , Pham Nhung H , Mai Bang H , Nguyen Tuan V , Nguyen Phuong T K , Le Nhan D , Huynh Tuan M , Anh Thu Le Thi , Chi Thanh Tran , Berglund Björn , Nilsson Lennart E , Bornefall Elin , Huu Song L , Stig-Inge. Hanberger Hakan
Published: October 2019

Background

Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC).

Methods

A point prevalence survey (PPS) with screening for colonization with CRE was conducted on 2233 patients admitted to neonatal, pediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of fecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome.

Results

A total of 1165 (52%) patients were colonized with CRE, most commonly Klebsiella pneumoniae (n = 805), Escherichia coli (n = 682) and Enterobacter spp. (n = 61). Duration of hospital stay, HAI, intubation, peripheral venous catheter and treatment with a carbapenem were independent risk factors for CRE colonization. The PPS showed that the prevalence of CRE colonization increased on average 4.2% per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5·5, P < 0·01) with CRE colonisation and HAI on admission.

Conclusion

These data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalized patients. CRE colonization places a major burden on the healthcare system due to the increased risk of HAI caused by CRE and associated increased mortality. This study shows that large-scale epidemiological surveillance of CRE using affordable methods is possible in low- and middle-income countries.

Disclosures

All authors: No reported disclosures.
506. Urinary Catheters Are Associated with Progression from Bacteriuria to Invasive Infections in Patients with Carbapenem-Resistant Enterobacteriaceae, Metropolitan Atlanta, 2011–2017
Authors: Howard-Anderson Jessica , Bower Chris W , Smith Gillian , Elizabeth Sexton Mary , Satola Sarah W , Farley Monica M , Jacob Jesse T
Published: October 2019

Background

Patients with carbapenem-resistant Enterobacteriaceae (CRE) bacteriuria have better outcomes than patients with an invasive CRE infection, but patients with bacteriuria may subsequently develop an invasive infection (“progression”). We sought to evaluate risk factors, particularly urinary catheters, for progression from CRE bacteriuria to an invasive CRE infection within one year.

Methods

We used population-based active surveillance data from the Georgia Emerging Infections Program to identify patients in metropolitan Atlanta with CRE in urine, but not in a concomitant or previous sterile site between August 1, 2011 and July 31, 2017. CRE was defined as an isolate resistant to tested third-generation cephalosporins and a minimum inhibitory concentration of ≥4 µg/mL for meropenem, doripenem or imipenem. We then assessed if these patients developed an invasive CRE infection (positive sterile site culture) with the same organism between one day and one year later. Demographics, culture site, comorbidities, and risk factors were obtained by chart review. Univariable analyses and multivariable logistic regression with progression as the outcome were performed in SAS 9.4.

Results

We identified 551 patients with CRE bacteriuria in 6 years, with an annual incidence of 1.1 cases/100,000 population. Many patients previously resided in long-term care facilities (48%), had a Charlson comorbidity index (CCI) >3 (38%), a central venous catheter (CVC, 34%) or a decubitus ulcer (27%, Table 1). Twenty-five patients (5%) progressed from CRE bacteriuria to an invasive CRE infection within one year (median 34 days). Predictors of progression in univariable analyses included the presence of a urinary catheter (OR 6.4 [95% CI: 1.9–21.6]), decubitus ulcer, CVC or other indwelling device, Klebsiella pneumoniae, black race, CCI >3, and ICU stay after urine culture was obtained (Table 2). In a multivariable analysis, urinary catheter (OR 4.6 [95% CI: 1.3–16.1]) predicted progression as well as K. pneumoniae, CCI >3 and CVC.

Conclusion

Progression from CRE bacteriuria to an invasive CRE infection is rare but clinically significant and is associated with urinary catheters. Future interventions should target urinary catheter removal, where possible, in patients with CRE bacteriuria.

Disclosures

All authors: No reported disclosures.
510. Exposure Investigation Following a Confirmed Case of Candida auris and Multiple Carbapenemase-Producing Carbapenem-Resistant Organisms
Authors: Nicholson Frances , Curless Melanie , Schiffhauer Maggie , Zhang Sean , Simner Patricia , Carroll Karen C , Rock Clare , Maragakis Lisa , Maragakis Lisa
Published: October 2019

Background

Co-infections of Candida auris and carbapenemase-producing carbapenem-resistant Gram-negative organisms (CP-CRO) are an increasing global concern and rarely seen in the United States. We report the case of a 59-year-old male, with recent hospitalization in India, admitted to our facility with C. auris isolated from urine and axilla/groin specimens and CP-CRO from five body sites.

Methods

Travel screening in the emergency department identified a patient at high risk for colonization/infection with multidrug-resistant organisms (MDRO). Contact precautions were initiated. Eight CP-CRO isolates were subsequently identified from clinical and routine surveillance cultures from five separate sites. Of the isolates, seven contained one or more carbapenemase-producing genes detected by Xpert Carba-R assay (Cepheid, Sunnyvale, CA) (Table 1). The microbiology laboratory alerted the infection control department of a presumptive positive C. auris from a clinical urine culture from the same patient. Enhanced mitigation strategies were initiated in regards to cleaning and disinfection.

An exposure investigation was also conducted using a point prevalence approach. Surveillance cultures were obtained from inpatients currently admitted to the same unit as the index patient. Axilla/groin specimens were collected for C. auris testing, and rectal specimens were collected for CP-CRO gene testing (CRE Real-Time PCR).

Results

Eighteen patients in addition to the index patient were hospitalized on the acute medicine unit. One patient refused testing for CP-CRO; therefore, 17 patients were tested for CP-CRO, and 18 patients were tested for C. auris. Neither CP-CRO nor C. auris were recovered from any patient.

Conclusion

A patient co-infected with C. auris and multiple CP-CRO was identified by clinical and routine surveillance cultures at Johns Hopkins Hospital. Travel screening allowed proactive isolation upon presentation. Enhanced infection control measures were implemented and a point prevalence surveillance study was conducted on the general acute care medicine inpatient unit. No transmission of either C. auris or CP-CRO was detected, likely due in part to rapid identification and strict infection control measures.

Disclosures

All authors: No reported disclosures.
521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa
Authors: Patel Twisha S , Kaye Keith S , Krishnan Jay , Marshall Vince , Mills John , Albin Owen , Young Carol , Smith Aaron , Lephart Paul , M. Pogue Jason
Published: October 2019

Background

Meropenem/vaborbactam (MV) is a carbapenem and boronic acid–based β-lactamase inhibitor combination product with potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. As carbapenem resistance in Pseudomonas aeruginosa (PSA) is primarily driven by porin mutations, efflux pumps, or infrequently by metallo-β-lactamases, vaborbactam is not expected to improve the in vitro activity of meropenem (MEM) against this pathogen. However, limited data currently exists assessing the comparative in vitro activity of MEM and MV. The purpose of this study was to compare the in vitro activity of MV and MEM against a large real-world sample of clinical isolates of PSA where both MV and MEM are routinely tested on all isolates.

Methods

All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) were determined using TREK broth microdilution panels and isolates were considered susceptible to MV if the MIC was ≤4 mg/L and MEM if the MIC was ≤2 mg/L.

Results

A total of 2,967 isolates of PSA from clinical specimens were included. 80.5% of isolates were susceptible to MEM (MIC50 ≤1 mg/L and MIC90 8 mg/L, range ≤1 to >32 mg/L) at a breakpoint of ≤2 mg/L and 86.3% at a breakpoint of ≤4 mg/L; whereas 90.8% of isolates were susceptible to MV (MIC50 ≤1 mg/L and MIC90 4 mg/L, range ≤1 to >8 mg/L). Of those displaying MEM MIC >2 mg/L, 53% (n = 308) were susceptible to MV. Of those displaying MEM MIC >4 mg/L, 33.7% (n = 137) were susceptible to MV. Although the majority of MIC discordances in MEM-R/MV-S isolates were 1–2 doubling dilutions, 52 (38%) isolates had their meropenem MIC decreased ≥3 doubling dilutions by the addition of vaborbactam suggesting significant inhibitory activity (Table 1).

Conclusion

We found a surprising number of PSA isolates with discordant MV and MEM susceptibility at Michigan Medicine. Further exploration of mechanisms of meropenem resistance in these isolates is warranted.

Disclosures

All authors: No reported disclosures.
540. The Impact of Diet and Oral Hygiene on the Risk of Multidrug-Resistant Organism Carriage in the Mouth and Gut
Authors: Kates Ashley , Watson Lauren , Mares Julie , Christensen Krista , Kalan Lindsay , Malecki Kristen , Peppard Paul , Sethi Ajay , Safdar Nasia
Published: October 2019

Background

Little is known about the relationship between oral hygiene and multidrug-resistant organism in the mouth and gut. We aimed to assess the relationship of oral hygiene and diet with multidrug-resistant organism (MDRO) carriage in the oral cavity and gut.

Methods

Participants were adults over age 18 from the 2016–2017 Survey of the Health of Wisconsin (SHOW) and its ancillary Wisconsin Microbiome Study. SHOW surveys residents of Wisconsin, collecting health determinants including a food frequency questionnaire, oral health, as well as biologic specimens. MDROs were defined as the presence of methicillin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus, and Fluoroquinolone-resistant Gram-negative bacteria identified via culture from saliva, oral swabs, and stool samples. Statistical analysis was performed in R v3.5.1. Univariate analyses were conducted for all variables in the data set. Any variable with a P-value < 0.2 in the univariate analysis was considered for the logistic regression. Logistic regression using the glm function was done modeling MDRO carriage in either the saliva, oral swab, saliva and oral samples combined, and stool against diet, oral health, and known confounders.

Results

876 participants were included in the dataset with all 876 providing oral and stool samples and 784 providing saliva samples. Thirty-three patients were MDRO positive in the saliva (4.2%), 36 were positive in the oral swabs (4.1%), 55 were positive in either the saliva or oral swabs (6.3%), and 103 were positive in the stool (11.8%). In the logistic regression, consumption of whole grains was significantly associated with reduced MDRO carriage in the saliva (P = 0.046) and saliva and oral swab combined (P = 0.036) data sets (Table 1).

Conclusion

Consuming more whole grains was associated with a lower prevalence of MDRO carriage in the oral cavity. Higher levels of sugar consumption were associated with a higher prevalence of MDRO in the gut. Oral hygiene was not found to be associated with MDRO colonization in the mouth and a higher prevalence in the gut in this cross-sectional study. This may be due to over-reporting of hygiene practices by participants. Being positive for an MDRO in the oral cavity significantly increased the risk of MDRO carriage in the gut.

Disclosures

All authors: No reported disclosures.
549. First Report for Emergence of Chromosomal Borne Colistin Resistance Gene mcr-1 in a Clinical Acinetobacter Baumannii Isolates from India
Authors: RAHMAN MOHIBUR , Ahmad Saheem
Published: October 2019

Background

Efficacy of Colistin the last line agent against infections due to multidrug-resistant (MDR) gram-negative pathogens, has been challenged when Liu et al. reported a plasmid-mediated gene, mcr-1, in 2015. Thereby this plasmid-borne mcr has been reported in bacterial isolates worldwide taken from humans, animals, farms, foods, and the environment. The present work invesitigate the mcr gene among clinical isolates of Acinetobacter Baumannii at our tertiary referral hospital of India.

Methods

The study was conducted at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. MIC values for 100 consecutive non-duplicate MDR isolates of Acinetobacter were checked for Colistin. PCR amplification of mcr gene was performed followed by sequencing of the amplicons. Clinical features of patients infected with mcr positive isolates were unveiled. Clonal relatedness of these isolates was investigated by Pulsed-field gel electrophoresis (PFGE). The mcr-1 localization was checked by conjugation followed by PFGE southern hybridization.

Results

20/100 (20%) isolates were colistin resistant with having MIC Values of more than 8≤ µg/mL. The 20 colistin resistances isolates were PCR positive for mcr-1 and had been assigned EMBL/GeneBank nucleotide accession numbers MH730099-MH730118. Oher antibiotic resistance gene like ESBL, NDM-1, VIM, and 16s rRNA methyl transferases like Arm A, rmtC, rmt F were also found in these isolates. Majority of these patients recovered from the infection (65%) after proper antibiotic therapy.The ISApl1 transposable elements were not detected in these isolates. These isolates were found clonally unrelated when analyze by pulsed-field gel electrophoresis. The conjugation attempt to transfer mcr-1 to recipient’s E. coli J53 failed, Southern hybridization showed that mcr-1 was found located on chromosome in multiple copies.

Conclusion

This is the first case of mcr-1 in a human clinical isolate in Acinetobacter Baumnnii from India. These findings highlight the vertical transferability of colistin resistance by mcr-1 gene in Acinetobacter Baumnnii with the association of known some unknown insertion sequence located on chromosome. Strategies required to contain their spread and evolution of such genes.

Disclosures

All authors: No reported disclosures.
550. Carbapenem--Resistant E. coli and A. baumannii Among Catheter-Related Blood Stream Infection Patients in Egyptian ICUs
Authors: Elmanakhly Arwa R , Kholy Amani
Published: October 2019

Background

The spreading of E. coli and A. baumannii in hospitals is a growing concern due to increased resistance to carbapenems and Fluoroquinolones. The present study aimed to specifically evaluate the presence of mutations in the gyrA and parC genes in Egyptian ICU and their correlation with carbapenem-resistant genes E. coli and A. baumannii isolates from patients in 4 tertiary care hospital in Egypt.

Methods

A total of 120 A. baumannii and E. coli clinical isolates were isolated from ICU patients in 4 tertiary hospitals in Egypt. The bacterial isolates were identified by VITEK-2 (Bio Merieux, France). Antimicrobial susceptibility testing was performed according to CLSI guidelines. Phenotypic detection of carbapenemase activity was done by carba-NP test, followed by molecular identification of carbapenemase encoding genes blaNDM, blaOXA-48 and blaKPC by multiplex PCR. The quinolone resistance-determining regions (QRDRs) of gyrA and parC genes were amplified by singleplex PCR followed by reverse and forward sequencing to detect the gene mutation. The DNA sequences were compared with the sequences of wild type of these genes available in GenBank database. Then, the obtained DNA sequences and their amino acid sequences were analyzed using bioinformatics tools.

Results

All isolates showed a high level of resistance among tested antimicrobial agents (cephalosporins, aminoglycosides, carbapenems, penicillins) that ranged from 36% to 100%. Carba-NP detected 43.59% of the carbapenem-resistant isolates. Multiplex PCR detected that 17.95%, 46.15% and 2.56% of isolates were harboring blaKPC, blaNDM and blaOXA-48 respectively. PCR and sequencing technique showed combined gene mutation in 8 carbapenem-resistant E. coli and A. baumannii isolates. The specific substitutions observed in gyrA were Cys173Arg, Cys174 Gly, Asp80Val, Tyr178ASP, Tyr84Gly, Glu85Lys, Ser172Leu and Asp176Asn. While, the specific substitutions observed in parC were point mutation 62 Arg, Phe60Leu, Ils66Val, Gln76Lys. Point mutation 62 Arg was observed in two A. baumannii isolates, whereas Ser172Leu mutation was observed in two E. coli isolates.

Conclusion

The presence of carbapenem resistance genes in combination with single and multiple mutations in QRDR causes the presence of highly resistant E. coli and A. baumannii isolates in the Egyptian hospitals.

Disclosures

All authors: No reported disclosures.