Safety and Efficacy of Ceftriaxone in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections: A Noninferiority Retrospective Cohort Study.

BACKGROUND: Antistaphylococcal penicillins and cefazolin are the treatments of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, requiring multiple doses daily. At Parkland, eligible uninsured patients with MSSA bloodstream infections (BSI) receive self-administered outpatient parenteral antimicrobial therapy (S-OPAT). Ceftriaxone was used in a cohort of S-OPAT patients for ease of once-daily dosing. OBJECTIVE: A retrospective study was conducted to evaluate clinical outcomes for patients discharged with ceftriaxone versus cefazolin to treat MSSA BSI. METHODS: A retrospective cohort noninferiority study design was used to assess treatment efficacy of ceftriaxone versus cefazolin among Parkland S-OPAT patients treated from April 2012 to March 2020. Demographic, clinical, and treatment-related adverse events data were collected. Clinical outcomes included treatment failure as defined by repeat positive blood culture or retreatment within 6 months, all-cause 30-day readmission rates, and central line-associated bloodstream infection (CLABSI) rates. RESULTS: Of 368 S-OPAT patients with MSSA BSI, 286 (77.7%) received cefazolin, and 82 (22.3%) received ceftriaxone. Demographics and comorbidities were similar for both groups. There were no treatment failures in the ceftriaxone group compared with 4 (1%) in the cefazolin group (P = 0.58). No difference in 30-day readmission rate between groups was found. The CLABSI rates were lower in ceftriaxone group (2%) compared with cefazolin (11%; P = 0.02). Limitations include retrospective cohort design. CONCLUSIONS: Ceftriaxone was found to be noninferior to cefazolin in this study. Our findings suggest that ceftriaxone is a safe and effective treatment of MSSA BSI secondary to osteoarticular or skin and soft tissue infections when used in the S-OPAT setting. POSTER ABSTRACT: OFID on 2018 Nov; 5(Suppl 1): S316: doi: 10.1093/ofid/ofy210.894.

Non-typeable Haemophilus influenzae and purpura fulminans.

Haemophilus influenzae typically causes illness and infection in the paediatric population. We report a case of a 53-year-old man who developed invasive non-typeable H. influenzae infection associated with purpura fulminans and multiorgan failure. On review of the literature, this is the first reported case of non-typeable H. influenzae causing purpura fulminans. The patient was treated with intravenous ceftriaxone 2 g/day and was eventually discharged from the hospital almost 2 months after admission. We discuss the role that infection/sepsis plays in disturbances to the coagulation cascade leading to purpura fulminans and the virulence factors that make non-typeable H. influenzae unique. Finally, we review other cases of H. influenzae associated with purpura fulminans and discuss the similarities with our case.

What's in a name? The heterogeneous clinical spectrum and prognostic factors in a cohort of adults with hemophagocytic lymphohistiocytosis.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) in adults is rare but frequently fatal. Diagnosis is often delayed and treatment approaches vary significantly in contrast to the protocol-driven approach typically used in pediatric HLH. To improve care of these complex patients, this study retrospectively examined the prevalence, clinical characteristics, therapies and outcomes of adult HLH patients at two large tertiary care centers. METHODS: Adult patients with HLH confirmed by retrospective review of electronic medical records using HLH2004 criteria during admissions to the University of Texas Southwestern and Parkland Memorial Hospitals between June 2007 and June 2017 were studied. RESULTS: Of 31 patients included, 67.7% were male with mean age of 46 years. Average time from admission to diagnosis was 10.5 days. 48% of patients had malignancy, with T-cell lymphoma being most common. Infections were seen in 70%. Autoimmune disorders were found in 9.6%. In total, 13 patients survived (44.8%). Median survival was 8 months with increased mortality in malignancy-associated HLH (median 0.56 months versus 36.5 months, p < 0.001). T-cell lymphoma carried a worse prognosis than other malignancies. Central nervous system disease, hypoalbuminemia, elevated bilirubin, elevated soluble interleukin 2 receptor, and elevated lactate dehydrogenase, were also associated with poor survival. Treatment varied significantly. No individual treatment improved survival. CONCLUSION: This study corroborates prior limited data in adult HLH patients regarding poor survival, particularly in malignancy-associated HLH. Earlier recognition of this disease and a multidisciplinary approach to streamline diagnosis and optimize treatment are needed to improve outcomes in adult HLH patients.

Effectiveness of direct-acting antiviral therapy for hepatitis C in difficult-to-treat patients in a safety-net health system: a retrospective cohort study.

BACKGROUND: Direct-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort. METHODS: This retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up. RESULTS: DAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16-0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up. CONCLUSIONS: Effective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems.

Opt-out HIV and Hepatitis C Testing at the Dallas County Jail: Uptake, Prevalence, and Demographic Characteristics of Testers.

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are common in the criminal justice system. We offered opt-out HIV/HCV testing at the Dallas County Jail during intake from June 2015 to November 2016, after which testing was integrated into routine phlebotomy processes. The uptake of testing increased from 12.9% (118/915) in June 2015 to 80.5% (269/334) in January 2016. HIV was confirmed in 1.0% (30/3155) of inmates; 6 were new diagnoses and all were linked to care. HCV antibody positivity was found in 16.4% (500/4042) of inmates. Sixty percent (155/258) of HCV-positive inmates born between 1945 and 1965 (ie, baby boomers) were non-Hispanic black, whereas 56.2% (136/242) born after 1965 were non-Hispanic white. Testing only baby boomers would have missed approximately half of HCV infections, predominantly among young, non-Hispanic white people. Future efforts should expand HIV and HCV testing in jails, as it is feasible, acceptable, and increases prevention and engagement in care for a high-prevalence, hard-to-reach population.

Cryopreservation modulates the detection of regulatory T cell markers.

BACKGROUND: Regulatory T cells (Tregs) modulate the host response in infectious diseases and are key mediators of peripheral tolerance. Cryopreservation of peripheral blood mononuclear cells (PBMCs) is commonly used in immunological field studies where access to complex laboratory tests is not feasible. Our objective is to assess the effects of cryopreservation on the flow cytometric detection of surface and intracellular markers of Tregs. METHODS: Heparinized venous blood was obtained from 36 healthy individuals and 15 HIV-1 infected subjects. PBMCs were isolated and stained for surface and intracellular markers of Tregs. PBMCs from each subject were cryopreserved in liquid nitrogen with DMSO; these cells were thawed and stained at a later date. All samples were analyzed by flow cytometry. The proportion of Tregs was compared using Wilcoxon signed-rank test. RESULTS: Cryopreservation decreased the proportion of Tregs identified by surface and intracellular markers in healthy individuals and in HIV-1 patients. The proportion of CD4+CD25+FoxP3+ was decreased from 3.13 to 2.16% (P < 0.001) for non-HIV subjects and from 2.68 to 0.94% (P < 0.001) for HIV subjects, compared to fresh samples. Significant reduction was also observed for CD4+CD25+CD127lo-neg. However, the effect varied considerably between samples. The effect was similar among HIV and non-HIV patients (P = 0.38). CONCLUSIONS: Cryopreservation modulates the detection of surface and intracellular markers of Tregs. These results confirm that research on Tregs, including studies of HIV-1 infected patients, should be carried out prospectively on fresh samples in order to obtain unbiased conclusions. Results using cryopreserved cells should be regarded as only preliminary.