Objectives: Rapid fluid resuscitation has become standard in sepsis care, despite “low-quality” evidence and absence of guidelines for populations “at risk” for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived “at-risk” volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume “overload” by bedside examination. Design: Retrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics. Setting: Urban, tertiary care center between January 1, 2014, and May 31, 2017. Patients: Emergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock. Interventions: Administration of IV fluids by bolus. Measurements and Main Results: In total, 509 patients received 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% mortality in the shock group. Patients who were elderly (odds ratio, 0.62; 95% CI, 0.46–0.83), male (odds ratio, 0.66; CI, 0.49–0.87), obese (odds ratio, 0.18; CI, 0.13–0.25), or with end-stage renal disease (odds ratio, 0.23; CI, 0.13–0.40), heart failure (odds ratio, 0.42; CI, 0.29–0.60), or documented volume “overload” (odds ratio, 0.30; CI, 0.20–0.45) were less likely to achieve 30by3. Failure to meet 30by3 had increased odds of mortality (odds ratio, 1.52; CI, 1.03–2.24), delayed hypotension (odds ratio, 1.42; CI, 1.02–1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5–3.6), without differential effects for “at-risk” groups. Higher fluid volumes administered by 3 hours correlated with decreased mortality, with a plateau effect between 35 and 45 mL/kg (p < 0.05). Conclusions: Failure to reach 30by3 was associated with increased odds of in-hospital mortality, irrespective of comorbidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These findings are retrospective and require future validation.

Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections.

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD.

Addition of lactate to the critical result laboratory's call list did not lead to a statistically significant improvement in time to IVFs or antibiotics, although the average time to antibiotics and IVFs decreased by 51.1 and 68.4 minutes, respectively. Hospital mortality, 30-day mortality, and 90-day mortality were lower in group 2, which may be, in part, due to increased recognition of severe sepsis by critical result notification and earlier intervention.

Sudden unexplained death in epilepsy (SUDEP) refers to a death in a patient with epilepsy that is not due to trauma, drowning, status epilepticus, or another apparent cause. Although the pathophysiology of SUDEP is incompletely understood, growing evidence supports the role of seizure-associated arrhythmias as a potential etiology. We present a unique case of a patient presenting with ventricular tachycardia shortly following a seizure, along with corresponding laboratory data. Awareness of high risk arrhythmias in seizure patients could lead to advances in understanding pathophysiology and treatment of this complication of seizure disorder and ultimately prevention of SUDEP.