Successful Treatment of Persistent Coronavirus Disease 2019 Infection in a Patient With Hypogammaglobulinemia With REGN-COV2: A Case Report.

A 55-year-old man with hypogammaglobulinemia due to previous rituximab treatment developed persistent coronavirus disease 2019 pneumonia. Treatment with REGN-COV2 (casirivimab and imdevimab) resulted in the clearance of the infection. Targeted antiviral antibodies may be an important weapon in the management of immunocompromised patients infected with severe acute respiratory syndrome coronavirus 2 who fail to mount an immune response.

Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2.

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).

H1N1 Influenza Causing Fulminant Myocarditis Requiring Extracorporeal Membrane Oxygenation.

Influenza infection is a known cause of global morbidity and mortality. Most cases of influenza A (H1N1) influenza infection are mild and do not require hospitalization. Although the most common presentation is with upper respiratory tract symptoms, hemodynamic instability requiring vasoactive drugs and ventilatory support use is unusual. We present a case of acute fulminant myocarditis that presented with dyspnea, which was confirmed with laboratory tests, chest X-ray, and echocardiogram. The test for H1N1 in nasopharyngeal secretions was positive. The patient evolved to refractory cardiogenic shock despite the clinical measures applied.

Clinical outcomes of carbapenem-resistant Acinetobacter baumannii bloodstream infections: study of a 2-state monoclonal outbreak.

OBJECTIVE: To characterize the clinical outcomes of patients with bloodstream infection caused by carbapenem-resistant Acinetobacter baumannii during a 2-state monoclonal outbreak. DESIGN: Multicenter observational study. Setting. Four tertiary care hospitals and 1 long-term acute care hospital. METHODS: A retrospective medical chart review was conducted for all consecutive patients during the period January 1, 2005, through April 30, 2006, for whom 1 or more blood cultures yielded carbapenem-resistant A. baumannii. RESULTS: We identified 86 patients from the 16-month study period. Their mortality rate was 41%; of the 35 patients who died, one-third (13) had positive blood culture results for carbapenem-resistant A. baumannii at the time of death. Risk factors associated with mortality were intensive care unit stay, malignancy, and presence of fever and/or hypotension at the time blood sample for culture was obtained. Only 5 patients received adequate empirical antibiotic treatment, but the choice of treatment did not affect mortality. Fifty-seven patients (66.2%) had a single positive blood culture result for carbapenem-resistant A. baumannii; the only factor associated with a single positive blood culture result was the presence of decubitus ulcers. Interestingly, during the study period, a transition from single to multiple positive blood culture results was observed. Four patients, 3 of whom were in a burn intensive care unit, were bacteremic for more than 30 days (range, 36-86 days). CONCLUSIONS: To our knowledge, this is the first time a study has described 2 patterns of bloodstream infection with A. baumannii: single versus multiple positive blood culture results, as well as a subset of patients with prolonged bacteremia.

Impact of the implementation of a sepsis protocol for the management of fluid-refractory septic shock: A single-center, before-and-after study.

BACKGROUND: Evidence-based guidelines have been published for the acute management of severe sepsis and septic shock. Key goals of institution-driven protocols include timely fluid resuscitation and antibiotic selection, as well as source control. OBJECTIVE: This study assessed the impact of a sepsis protocol on the timeliness of antibiotic administration, the adequacy of fluid resuscitation, and 28-day mortality in patients with fluid-refractory septic shock. METHODS: This was a single-center, before-and-after study (18 months before July 2007 and 18 months after) with prospective data collection evaluating the outcomes of a sepsis protocol in adult patients with fluid-refractory septic shock. All patients received a fluid challenge and antibiotics; those who did not were excluded from this analysis. Preprotocol findings led to the development of the sepsis protocol, which emphasized fluid resuscitation, timely administration of antibiotic therapy, and collection of specimens for culture at the onset of septic shock. In the pre- and postprotocol phases of the study, data were collected prospectively and analyzed for demographic characteristics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured prospectively at any time during the patient's hospital admission. The primary end points were the time to administration of antimicrobial therapy and the appropriateness of fluid resuscitation before and after implementation of the sepsis protocol. RESULTS: A total of 118 patients were included in the analysis: 64 and 54 in the pre- and postprotocol groups, respectively. Patients in the preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of 61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the postprotocol group were primarily men (54% [29/54]) and had a mean age of 52 (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis protocol resulted in a greater percentage of patients receiving timely antibiotic therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001) compared with the preprotocol group. Post hoc analysis found significant decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital mortality was not significantly different between the groups (survival 46% [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for predictors of in-hospital mortality identified an interval between shock and empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI, 1.91-16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01-1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05-0.61; P = 0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64) to 33% (18/54) after implementation of the protocol (P = 0.004). CONCLUSION: Implementation of a sepsis protocol emphasizing early administration of antibiotic therapy and adequate fluid resuscitation was associated with improved clinical outcomes and lower 28-day mortality in patients with fluid-refractory septic shock at this institution.

PG-M/versican binds to P-selectin glycoprotein ligand-1 and mediates leukocyte aggregation.

P-selectin glycoprotein ligand-1 (PSGL-1), a glycoprotein expressed on the cell surface of leukocytes, binds to selectins and mediates leukocyte rolling on the vascular endothelium. Here we report that PSGL-1 binds to the C-terminal (G3 domain) of the extracellular proteoglycan PG-M/versican. Cells transfected with PSGL-1 or a shorter form containing the binding site, or cells expressing endogenous PSGL-1 aggregate in the presence of versican or G3 product. The aggregation appears to be induced by G3 multimers that bind to PSGL-1 and form a network. Endogenous versican and/or G3-containing fragments also bind to PSGL-1 in human plasma. Removal of the endogenous G3-containing fragments reduces the effect of plasma on leukocyte aggregation. Finally, the roles of G3-containing fragments in leukocyte aggregation were confirmed in a mouse model. Taken together, our results strongly support a physiologically relevant role for PSGL-1/versican binding and may have implications in the immunoresponse.