The Clinical Impact of Metagenomic Next-Generation Sequencing (mNGS) Test in Hospitalized Patients with Suspected Sepsis: A Multicenter Prospective Study.

Background:Next Generation Sequencing (NGS) is a newly developed technology and able to detect pathogens rapidly, which may have great importance in early diagnosis and clinical management of infectious diseases. Our study aimed to assess the diagnostic performance and clinical impact of metagenomic NGS (mNGS) in hospitalized patients with suspected sepsis and analyze the suitable population for mNGS test besides culture.Methods:A multi-center, prospective cohort study was performed. We enrolled eligible patients with hospitalized infection, collected demographic and clinical characteristics, and record the 30-day survival. Blood samples were collected on the day of enrollment to perform blood culture and mNGS test. Diagnostic efficacy of mNGS test and blood culture were calculated, and clinical impact of antibiotic regimen modification based on pathogenic test were also analyzed with SPSS22.0 (SPSS Inc, Chicago, IL).Results:We collected demographic and clinical characteristics of patients, and record the 30-day survival. Blood samples were collected on the day of enrollment to perform blood culture and mNGS test. Diagnostic efficacy of mNGS test and blood culture were calculated, and clinical impact of antibiotic regimen modification based on pathogenic test were also analyzed. A total of 277 patients were enrolled and 162 were diagnosed with sepsis. Among patients with 30-day follow-up data, the mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time [27.0(26.0, 29.0) vs 96.0(72.0, 140.3) hours, P < 0.001] and higher sensitivity (90.54% vs 36.00%, P < 0.001) than blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotics use, and early stage of infection than blood culture. Higher reads of pathogens detected by mNGS was related to 30-day mortality (P=0.002). The mNGS test was capable of guiding antibiotic regimen modification and ameliorating prognosis. Negative mNGS results helped with antibiotic de-escalation safely.Conclusions mNGS technology may be helpful for patients with possible blood-stream infections, especially in fungal infection and for patients with mild symptoms, prior antibiotics use and early stage of infection. Its role in antibiotic stewardship and ameliorating prognosis warrants further study.Trial registrationThe study was registered on the Chinese Clinical Trial Registry (Number: ChiCTR1800019187) on 01/24/2019 (Retrospectively registered).

1022. Impact of Hospitalization on Antiretroviral Therapy for People Living with HIV

Background Persons living with HIV (PLWH) are frequently hospitalized for reasons often unrelated to HIV. Transitioning of antiretroviral therapy (ART) while inpatient may not always be an immediate priority due to lack of knowledge, formulary restrictions, and patient status. This could lead to medication errors and gaps in therapy, which can persist at discharge, and could lead to viral rebound and disease progression. The purpose of this study was to identify effects of hospitalization on ART for PLWH. Methods This was an IRB approved, multi-center, retrospective cohort study of patients with HIV and/or AIDS based on ICD codes. Patients were included if they were at least 18 years old, receiving outpatient ART prior to admission, and hospitalized between March 2016 and March 2018. Patients were excluded if they were pregnant and only received intravenous zidovudine during their hospitalization. The primary objective was to determine the rate of ART restarted during hospitalization. Secondary objectives included rate at which inpatient ART was modified compared to outpatient regimen, and risk factors associated with regimen modification. Results Of 400 patients screened, 295 (74%) patients were on an outpatient ART regimen and were included in the study. Approximately half, 51%, were on a single tablet regimen (STR) outpatient. This population was majority male (59%) and of black race (87%). Median age was 49 years. Median CD4 count was 160 cells/mm3, while median HIV RNA for those with detectable viral load was 57,095 copies/mL. 236 of 295 patients (80%) received ART during their inpatient stay. However, 70 (30%) of these patients received a regimen that differed from their outpatient ART regimen. 69% of regimens were modified for reasons other than to optimize therapy. Patient sex, place of admission, and receipt of a STR or multi-tablet regimen (MTR) as an outpatient did not significantly impact rate of regimen modification. Conclusion Ensuring appropriate transition of ART during hospitalization remains an area in need of improvement. No one specific factor was associated with whether outpatient ART was appropriately and accurately restarted during hospitalization. Thus, there are many opportunities to improve transitions of care and antiretroviral stewardship. Disclosures All Authors: No reported disclosures

Rate of Initial Anti-retroviral Treatment Modification and Its Predictors Among Adult Hiv/aids Patients at Pawe General Hospital, Benishangul Gumuz Region, Northwest Ethiopia

Background: Combination antiretroviral therapy (cART) is the cornerstone of managing patients with HIV infection. Once cART is initiated, patients generally remain on medications indefinitely. However, antiretroviral regimens commonly require changes which often involve switches of multiple medications simultaneously. The maximal regimen durability with regard to safety and efficacy is a critical factor for long-term success of ART since modification to cART has a number of challenges.Objectives: To assess the rate, time to change, reasons and predictors of treatment modification among HIV/AIDS patients at Pawe General Hospital.Method: Hospital based retrospective cohort study was conducted among adult HIV/AIDS patients on follow-up in Pawe Hospital from 01 April 2017 to 30 April 2017. Patients who started cART at Pawe General Hospital from January 2012 to December 2016 were included. Data abstraction tool was used to collect data from patient chart. Data were analyzed using SPSS version 21. Descriptive statistics were used to summarize patient socio-demographics characteristics and rate of regimen modification. Bivariate and multivariate Cox proportional hazard were performed to identify the predictors. Result: Over a median follow-up period of 21 months (IQR 6 - 38), 62 (14.5%) patients modified their initial regimens (incidence rate (IR); 7.66 per 100 person years [95% CI: 5.84 – 9.50]). Toxicity was the most common reason (72.6%). In multivariate Cox regression model, WHO stage III/IV at initiation(AHR;2.39, 95% CI: 1.23 – 4.66), AZT based initial NRTI backbone (AHR; 8.19, 95% CI: 4.55 - 14.73), low baseline hemoglobin ((< 7 g/dl [AHR; 6.32, 95% CI: 1.40 – 28.58] and 7-9.9 g/dl [AHR 4.21, 95% CI: 1.92 - 9.22]) and co-medication with cART (AHR 1.73, 95% CI: 1.03 - 2.89) were associated with increased risk of treatment modification.Conclusion: Initial regimen modification rate was lower in this population than cohorts in resource-rich settings. Special attention should be given for patients who are at advanced disease stage, AZT based regimen, low baseline hemoglobin and taking additional medications other than cART.

Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work

Background: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5–7%, and the percentage of positive patients admitted to intensive care units being 9–11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.

Metabolic Complications and Kidney Transplantation: Focus on Glycaemia and Dyslipidaemia

Post-transplant diabetes mellitus (PTDM) and dyslipidaemia are the most common metabolic complications in kidney transplant recipients (KTR). They are associated with a higher risk of lower graft function and survival, as well as an increased risk of cardiovascular disease (CVD). The aim of this review is to provide current data on the epidemiology, pathophysiology and optimal management of these two principal metabolic complications in KTR. Several risk factors in this metabolic milieu are either already present or emerge after renal transplantation, such as those due to immunosuppressive therapy. However, the exact pathogenic mechanisms have not been fully elucidated. Awareness of these disorders is crucial to estimate CVD risk in KTR and optimize screening and therapeutic strategies. These include lifestyle (preferably according to the Mediterranean pattern) and immunosuppressive regimen modification, as well as the best available anti-diabetic (insulin or oral hypoglycaemic agents) and hypolipidaemic (e.g. statins) regimen according to an individual’s metabolic profile and medical history.

Penanganan Tuberkulosis Resistan Obat pada Daerah Terpencil: Mission Impossible?

Background: Complicated drug-resistant Tuberculosis (TB) management becomes a distinctive challenge for health care provider in rural area. Case: We reported 6 drug-resistant TB cases that were found in Sikka Regency, East Nusa Tenggara, based on rapid molecular test. Each case had unique problem which needs specific management, such as difference between the conventional and rapid drug susceptibility test, appearance of second line injection drug resistant (Pre-XDR TB), Human Immunodeficiency Virus (HIV) co-infection, emergence of serious acute psychosis side effect, and the drop out management. Discussion: We will discuss the management of each individual’s problem that arises during the antitubercular treatment monitoring and the requiring regimen modification under the national guideline. Conclusion: Drug-resistant TB management is a very complex matter. However, with sustainable effort, commitment, and collaboration between referral center and health care provider in rural area, guidelin be appropriate management could be achieved. Despite its possibility, prevention of resistant TB should have been done as early as possible, one of them is completion of regular TB treatment.

Colon Surgery Risk With Corticosteroids Versus Immunomodulators or Biologics in Inflammatory Bowel Disease Patients With Clostridium difficile Infection

Background Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), and CDI often precipitates IBD exacerbation. Because CDI cannot be distinguished clinically from an IBD exacerbation, management is difficult. We aimed to assess factors associated with adverse outcomes in IBD with CDI, including the role of escalating or de-escalating IBD therapy and CDI treatment. Methods Records for patients with IBD and CDI from 2008 to 2013 were abstracted for variables including IBD severity before CDI diagnosis, CDI management, subsequent IBD exacerbation, CDI recurrence, and colon surgery. Colon surgery was defined as resection of any colonic segment within 1 year after CDI diagnosis. Results We included 137 IBD patients (median age, 46 years; 55% women): 70 with ulcerative colitis (51%), 63 with Crohn’s disease (46%), and 4 with indeterminate colitis (3%). Overall, 70% of CDIs were mild-moderate, 14% were severe, and 15% were severe-complicated. Clostridium difficile infection treatment choice did not vary by infection severity (P = 0.27). Corticosteroid escalation (odds ratio [OR], 5.94; 95% confidence interval [CI], 2.03–17.44) was a positive predictor of colon surgery within 1 year after CDI; older age (OR, 0.09; 95% CI, 0.01–0.44) was a negative predictor. Modifying the corticosteroid regimen did not affect CDI recurrence or risk of future IBD exacerbation. Adverse outcomes did not differ with CDI antibiotic regimens or biologic or immunomodulator regimen modification. Conclusions Corticosteroid escalation for IBD during CDI was associated with higher risk of colon surgery. Type of CDI treatment did not influence IBD outcomes. Prospective studies are needed to further elucidate optimal management in this high-risk population.

Modification of Initial Highly Active Antiretroviral Therapy (HAART) Regimen in Paediatric HIV Patients

Background:Treatment options among Human Immunodeficiency Virus (HIV)-infected children are limited as only a few Highly Active Antiretroviral Therapy (HAART) are approved worldwide for paediatric use. Among children, frequent changes in HAART regimen can rapidly exhaust treatment options, and information addressing this issue is scarce.Objective:The aim of the study was to determine factors associated with the modification of initial HAART regimen modification among HIV-infected children.Method:A retrospective study was performed among HIV-infected children aged 18 and below, that received HAART for at least six months in a tertiary hospital in Malaysia. Factors associated with modification of initial HAART regimen were investigated.Results:Out of 99 patients, 71.1% (n=71) required initial HAART regime modification. The most common reason for HAART modification was treatment failure (n=39, 54.9%). Other reasons included drug toxicity (n=14, 19.7%), change to fixed-dose products (n=11, 15.5%), product discontinuation (n=4, 5.6%) and intolerable taste (n=3, 4.2%). The overall mean time retention on initial HAART before regimen modification was 3.32 year ± 2.24 years (95% CI, 2.79–3.85). Patient's adherence was the only factor associated with initial regimen modification in this study. Participants with poor adherence showed a five-fold risk of having their initial HAART regimen modified compared to those with good adherence (adjusted OR [95% CI], 5.250 [1.614 – 17.076], p = 0.006).Conclusion:Poor adherence was significantly associated with initial regimen modification, intervention to improve patient's adherence is necessary to prevent multiple regimen modification among HIV-infected children.

Confirmation of factors that influence antiretroviral regimen change and the subsequent patient outcomes at a Regional Hospital in rural KwaZulu-Natal

Background: Treatment failure (TF) and adverse drug reactions (ADRs) are the main indications for antiretroviral therapy (ART) regimen change. Identification of factors influencing regimen change and subsequent health outcomes of patients after regimen change is essential in providing a sustainable and effective antiretroviral roll-out campaign.Aim: To confirm the factors that influence antiretroviral regimen change and to evaluate patient outcomes post regimen change.Methods: A retrospective chart analysis of 269 HIV-infected non-pregnant patients (age >18 years), who underwent an antiretroviral (ARV) regimen change and were followed up for approximately one year since initiation, was undertaken at a Provincial Hospital ARV Clinic in KwaZulu-Natal, from January 2008 to December 2012.Results: Of the 269 patients, there were 200 females (75%). Most patients were between the ages 30 and 44 (57.6%). Only five patients had coexisting tuberculosis (TB) infection (2%). The most common first-line ART regimen to be changed was stavudine (D4T)/lamivudine(3TC)/ efavirenz(EFV) n = 111(41%). The most common regimen patients were changed to was tenofovir (TDF)/3TC/EFV n = 89(33%). Stavudine was the most commonly substituted drug (35.5%). Lipodystrophy was the most common ADR (56.8%). ADR was the indication for ART regimen change in 175 patients (65%), whilst TF accounted for ART regimen change in 94 patients (35%). Immunological success (CD4 counts) was shown after regimen change (374.21 ± 243.16 vs. 456.09 ± 250.07, CI: 0.95, p < 0.001). Undetectable viral loads were measured in 172/205 (83.9%) patients post regimen change.Conclusion: ADRs were the main cause for antiretroviral regimen change. Stavudine was the most substituted drug with lipodystrophy being the most common side effect. Coexisting TB infection did not influence regimen change. Immunological and virological success was shown after regimen modification.