Search

Abstract Background Polymyxin B hemoperfusion (PMX) removes endotoxin from septic shock patients. Although the treatment has been clinically used for more than 20 years, its cost-effectiveness has not been evaluated in detail. Methods This study used the Japanese diagnosis procedure combination (DPC) administrative database from April 2018 to March 2021. We selected adult patients with a primary diagnosis of sepsis and the SOFA score at the sepsis diagnosis was between 7 and 12. The patients were divided into the PMX group that received PMX treatment and the control group that did not receive PMX. After adjusting the patient background by propensity score matching, we calculated the incremental cost-effectiveness ratio (ICER) by determining the difference in quality-adjusted life-year (QALY) and medical cost between the PMX and the control groups. Results Nineteen thousand two hundred eighty-three patients were included in the study. Among them, 1492 patients received PMX treatment, and 17,791 did not. As a result of 1:3 propensity score matching, 965 patients in the PMX group and 2895 patients in the control group were selected and analyzed. Twenty-eight-day mortality and hospital mortality were significantly lower in the PMX group. The average medical cost per patient of the PMX group was 31,418 ± 21,144 Euro and that of the control group was 24,483 ± 21,762 Euro, with a difference of 6935 Euro. Life expectancy, life year-gained (LYG), and the QALY were 1.70, 0.86, and 0.60 years longer in the PMX group, respectively. The ICER was calculated to be 11,592 Euro/year, which was lower than the reported willingness-to-pay threshold of 38,462 Euro/year. Conclusion Polymyxin B hemoperfusion was shown to be an acceptable treatment in terms of the medical economy.

Background: Polymyxin B hemoperfusion (PMX) removes endotoxin from septic shock patients. Although the treatment has been clinically used for more than 20 years, its cost-effectiveness has not been evaluated in detail. Methods: This study used the Japanese diagnosis procedure combination (DPC) administrative database from April 2018 to March 2021. We selected adult patients with a primary diagnosis of sepsis and the SOFA score at the sepsis diagnosis was between 7 and 12. The patients were divided into the PMX group that received PMX treatment and the control group that did not receive PMX. After adjusting the patient background by propensity score matching, we calculated the incremental cost-effectiveness ratio (ICER) by determining the difference in quality-adjusted life-year (QALY) and medical cost between the PMX and the control groups. Results: Nineteen thousand two hundred eighty-three patients were included in the study. Among them, 1492 patients received PMX treatment, and 17,791 did not. As a result of 1:3 propensity score matching, 965 patients in the PMX group and 2895 patients in the control group were selected and analyzed. Twenty-eight-day mortality and hospital mortality were significantly lower in the PMX group. The average medical cost per patient of the PMX group was 31,418 ± 21,144 Euro and that of the control group was 24,483 ± 21,762 Euro, with a difference of 6935 Euro. Life expectancy, life year-gained (LYG), and the QALY were 1.70, 0.86, and 0.60 years longer in the PMX group, respectively. The ICER was calculated to be 11,592 Euro/year, which was lower than the reported willingness-to-pay threshold of 38,462 Euro/year. Conclusion: Polymyxin B hemoperfusion was shown to be an acceptable treatment in terms of the medical economy. [ABSTRACT FROM AUTHOR]

Abstract Background Polymyxin B hemoperfusion (PMX) aims to treat septic shock by removing endotoxin from the patient’s blood. However, the relationship between the severity of the patient's organ damage and the survival benefit of PMX treatment is not clear. Methods We analyzed the efficacy of PMX on adult sepsis patients using the propensity score matching method and the Japanese Diagnosis Procedure Combination (DPC) national inpatient database from April 2018 to March 2020. We stratified the patients into five categories based on their baseline Sequential Organ Failure Assessment (SOFA) score and compared the mortality between PMX-treated and non-treated groups in each category. We also compared continuous hemodiafiltration (CHDF)-, ventilator- and noradrenaline-free days between the groups. Results Of 44,177 patients included in the study, 2191 received PMX. After 1:1 propensity score matching, we created matched cohorts of 2033 pairs. PMX significantly improved the survival of the patients in the SOFA score categories of 7–9 and 10–12. On the other hand, there was no significant difference in the survival rate in SOFA score categories of 0–6, 13–15, and 16–24. In analyzing organ support-free days, PMX was also beneficial in the 7–9 and 10–12 SOFA categories compared to other categories. Conclusion Analysis of a large-scale Japanese inpatient database found a significant association between PMX efficacy and baseline SOFA score. This result indicates higher efficacy in patients with medium SOFA scores in the range of 7–12. The result provides a promising hypothesis for selecting appropriate patients for PMX and should be validated in future RCTs.

Background Sepsis and septic shock are formidable and complications in surgery with mortality 20–50%. In the pathogenesis of sepsis, a significant role belongs to bacterial endotoxin (LPS - liposaccharide).Aim of study Assessment of the efficacy of selective lipopolysaccharides hemosorption (SLH) in treatment of sepsis.Material and methods We examined 65 patients with developed sepsis or suspected presence of gram-negative infection. Patients were retrospectively divided into two groups. In Group 1, 27 patients received Polymyxin B hemoperfusion using Toraymyxin cartridges. In Group 2 (38 patients), adsorber Alteco (LPSA) was used.Results It was established that 28-day mortality was 11.1% in Polymyxin group and 28.9% in LPS group A, p = 0.091, 60-day mortality was 33.3 and 55.3%, respectively (p=0.065). The use of SLH contributed to a decrease in the activity of endotoxin (EAA) from 0.52 (0.39; 0.65) to 0.40 (0.36; 0.57) EU (p=0.330) in Polymyxin group and from 0.59 ( 0.42; 0.72) to 0.54 (0.40; 0.81) EU ( p = 0.981) in the LPS-A group. At the same time, the level of procalcitonin (PCT) in the blood statistically significantly decreased from 8.4 (3.6; 29.0) to 4.8 (1.9; 36.3) ng/ml (p=0.0117) only in the LPS-A group. The level of C-reactive protein (CRB) in the blood statistically significantly decreased only in the Polymyxin group, from 205 (154; 264) to 162 (106; 202) mg/L (p

Background: Polymyxin B hemoperfusion (PMX) aims to treat septic shock by removing endotoxin from the patient's blood. However, the relationship between the severity of the patient's organ damage and the survival benefit of PMX treatment is not clear. Methods: We analyzed the efficacy of PMX on adult sepsis patients using the propensity score matching method and the Japanese Diagnosis Procedure Combination (DPC) national inpatient database from April 2018 to March 2020. We stratified the patients into five categories based on their baseline Sequential Organ Failure Assessment (SOFA) score and compared the mortality between PMX-treated and non-treated groups in each category. We also compared continuous hemodiafiltration (CHDF)-, ventilator- and noradrenaline-free days between the groups. Results: Of 44,177 patients included in the study, 2191 received PMX. After 1:1 propensity score matching, we created matched cohorts of 2033 pairs. PMX significantly improved the survival of the patients in the SOFA score categories of 7–9 and 10–12. On the other hand, there was no significant difference in the survival rate in SOFA score categories of 0–6, 13–15, and 16–24. In analyzing organ support-free days, PMX was also beneficial in the 7–9 and 10–12 SOFA categories compared to other categories. Conclusion: Analysis of a large-scale Japanese inpatient database found a significant association between PMX efficacy and baseline SOFA score. This result indicates higher efficacy in patients with medium SOFA scores in the range of 7–12. The result provides a promising hypothesis for selecting appropriate patients for PMX and should be validated in future RCTs. [ABSTRACT FROM AUTHOR]

Introduction: Polymyxin B hemoperfusion (PMX) reduces endotoxin in septic shock patients' blood and can improve hemodynamics and organ functions. However, its effects on the reduction of septic shock mortality are controversial. Methods: Using the Japanese diagnosis procedure combination database from April 2016 to March 2019, we identified adult septic shock patients treated with noradrenaline. This study used propensity score matching to compare the outcome between PMX-treated and non-treated patients. The primary endpoint was 28-day mortality, counting from the day of noradrenaline initiation. The secondary endpoints were noradrenaline-, ventilator-, and continuous hemodiafiltration (CHDF)-free days at day 28. Results: Of 30,731 eligible patients, 4,766 received PMX. Propensity score matching produced a matched cohort of 4,141 pairs with well-balanced patient backgrounds. The 28-day survival rate was 77.9% in the PMX group and 71.1% in the control group (p < 0.0001). Median days of noradrenalin-, CHDF-, and ventilator-free days were 2 days (p < 0.0001), 2 days (p < 0.0001), and 6 days (p < 0.0001) longer in the PMX group than in the control group, respectively. When stratified with the maximum daily dose of noradrenaline, the PMX group showed a statistically significant survival benefit in the groups with noradrenaline dose <20 mg/day but not in the noradrenaline group dose ≥20 mg/day. Conclusion: Analysis of large Japanese databases showed that septic shock patients who received noradrenaline might benefit from PMX treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells. Methods We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28. Results Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups. Conclusion PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression. Trial registration ClinicalTrials.gov, NCT02413541. Registered on 3 March 2015.

Abstract Background Descending necrotizing mediastinitis is a common and progressive polymicrobial infection involving the neck and chest with a high death rate (10 to 40%). From a microbiological point of view, descending necrotizing mediastinitis is sustained by Gram-positive bacteria (43–62%), anaerobes (46–78%), and, rarely, Gram-negative bacteria. Data collected during the Antibiotic Resistance-Istituto Superiore di Sanità project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance. In particular, 32.9% of Klebsiella pneumoniae isolates were resistant to carbapenem, 33.6% of Staphylococcus aureus to methicillin, and 28.7% and 43.9% of Escherichia coli isolates to third-generation cephalosporins and fluoroquinolones, respectively. Case presentation We describe the case of a 38-year-old white man with septic shock due to descending necrotizing mediastinitis sustained by multidrug-resistant Gram-negative and Gram-positive bacteria treated after surgery with an IgM-enriched immunoglobulin preparation and polymyxin B hemoperfusion therapy. Conclusion Despite the contrasting data on the use of immunoglobulins and polymyxin B hemoperfusion in septic shock and the lack of literature in cases of acute mediastinitis caused by both Gram-negative and Gram-positive multidrug-resistant bacteria, we obtained an improvement in clinical conditions and the survival of our patient, against all odds.

Abstract Background The purpose of this study was to investigate whether polymyxin B hemoperfusion (PMX-HP) improves the survival of patients with septic shock. Methods This was a retrospective, multicenter study conducted on patients treated during a 3-year period. We performed propensity-score analyses of the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study database. The study included data on 1723 patients with septic shock aged 16 years or older. Furthermore, we divided patients into to PMX-HP- and non-PMX-HP-treated groups. The primary endpoint was all-cause hospital mortality; secondary endpoints included intensive care unit (ICU) mortality and number of ICU-free days (ICUFDs) in the first 28 days. Results Of 1,723 eligible patients, 522 had received PMX-HP. Propensity score matching created 262 matched pairs (i.e., 262 patients in each of the non-PMX-HP and PMX-HP groups). The proportion of all-cause hospital mortality was significantly lower in the PMX-HP group than in the non-PMX-HP group (32.8% vs. 41.2%; odds ratio (OR): 0.681; 95% confidence interval (CI): 0.470–0.987; P = 0.042). The number of ICUFD in the first 28 days was significantly higher in the PMX-HP group than in the non-PMX-HP group (18 (0-22) vs. 14 (0-22) days, respectively; P = 0.045). On the other hand, there was no significant difference in ICU mortality between the two groups (21.8% vs. 24.4%; OR: 0.844; CI: 0.548–1.300; P = 0.443). Conclusions Our results strongly suggest that PMX-HP reduces all-cause hospital mortality and length of ICU stay in patients with septic shock.

Capnocytophaga canimorsus is a Gram-negative bacterium, commonly found as a commensal germ in the oral cavity of dogs and cats. It is an opportunistic pathogen, but, in specific situations, it can cause very severe diseases, including arthritis, pleuritis, endocarditis, sepsis, and, in extremely rare cases, meningoencephalitis. The predisposing situations include immunosuppression, liver cirrhosis, splenectomy, hemochromatosis, beta thalassemia major (Cooley's anemia), and alcohol abuse. In this report, we describe the case of a 48-year-old male patient, with a medical history of several predisposing conditions, who developed a severe case of meningoencephalitis caused by C. canimorsus , following a dog bite on his hand. The patient was successfully treated for his meningitis, but subsequently he developed a hospital-acquired septic shock from Acinetobacter baumannii , which was treated with targeted antibiotic therapy and sequential extracorporeal blood purification therapies using Oxiris™ and Toraymyxin™ hemofilters., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, De Rosa et al.)

Background: The definition of sepsis was updated to sepsis-3 in February 2016. Currently, direct hemoperfusion therapy using the polymyxin B-immobilized fiber cartridge (PMX-DHP) is widely performed to treat sepsis and septic shock. However, the prognostic factors of PMX-DHPs in patients with sepsis using the new definition are unclear. We retrospectively assessed prognostic factors in patients who had received PMX-DHP therapy for sepsis and septic shock.Methods: We included 71 patients with severe infection who underwent PMX-DHP treatment from January 2006 to August 2015 in this study. Participants were re-evaluated according to the criteria of sepsis-3. The patients were divided into two groups based on having survived (n = 59) or not survived (n = 12) for 28 days after PMX-DHP treatment. Clinical data before and after PMX-DHP treatment were compared between the two groups.Results: Non-survivors showed a lower Glasgow Coma Scale (GCS) score before PMX-DHP treatment compared with 28-day survivors [12 (6-14) vs 14 (12-15), P < 0.01]. Furthermore, pH after the first PMX-DHP session was significantly lower in non-survivors than in survivors (7.28 ± 0.23 vs 7.39 ± 0.06, P = 0.03). Multivariate logistic regression analysis showed that only lower pH after the first PMX-DHP session was a predictor of 28-day mortality independent of age, sex, GCS score, and mean arterial pressure (odds ratio per pH of 0.01, 0.93; 95% confidence interval, 0.83-0.99; P = 0.02).Conclusion: The pH after the first PMX-DHP session is an independent risk factor for mortality in patients receiving PMX-DHP for sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Background/Aims: We assessed the survival benefit of polymyxin B hemoperfusion (PMX) in septic shock patients starting continuous renal replacement therapy (CRRT), who are known to have an increased rate of mortality. Methods: Adult patients in the Japanese diagnosis procedure combination database satisfying the following criteria were enrolled: hospitalized in 2007-2012; diagnosed as having sepsis; required noradrenaline and/or dopamine; and started CRRT in intensive care unit. Propensity scores for receiving PMX were created from patient and hospital characteristics. Results: Of 3,759 eligible patients, 1,068 received PMX. Propensity-score matching produced a matched cohort of 978 pairs. The 28-day mortality was 40.2% (393/978) in the PMX group and 46.8% (458/978) in the control group (p = 0.003). Logistic regression analysis revealed a significant association between the use of PMX and decreased 28-day mortality (adjusted OR 0.75; 95% CI 0.62-0.91). Conclusion: This large retrospective study suggests that septic shock patients starting CRRT may benefit from PMX. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of postoperative polymyxin B hemoperfusion on mortality in patients with abdominal septic shock triggered by lower gastrointestinal tract perforation, identifying subpopulations of patients who may benefit from this treatment. Design: Propensity-matched analysis. Setting: We used a nationwide inpatient database in Japan. Patients: We included patients who are 18 years old or older hospitalized during a period of 34 months between July 2007 and October 2011, who had open abdominal surgery on the day of admission (day 0) for perforation of lower gastrointestinal tract, and who required noradrenaline and/or dopamine. We excluded patients who died on day 0 or 1 and patients starting polymyxin B hemoperfusion on day 2 or later. Measurements and Main Results: The main outcome was 28-day mortality. Of 2,925 eligible patients, 642 received one or two polymyxin B hemoperfusion sessions, starting the first one on day 0 or 1. Propensity score matching created a matched cohort of 1,180 patients (590 pairs with and without polymyxin B hemoperfusion). The 28-day mortality was 17.1% (101 of 590) in the polymyxin B hemoperfusion group and 1 6.3% (96 of 590) in the control group (p = 0.696). Subgroup analyses by number of polymyxin B hemoperfusion sessions (one or two), timing of polymyxin B hemoperfusion initiation (day 0 or 1), the use of noradrenaline, and number of dysfunctional organs (one to six) did not show any significant difference in 28-day mortality between the groups. Multiple logistic did not show a significant association between the use of polymyxin B hemoperfusion and 28-day mortality (adjusted odds ratio, 1.10; 95% CI, 0.80-1.51; p = 0.569). Age, end-stage renal disease requiring maintenance hemodialysis, the use of noradrenaline, and number of dysfunctional organs were positively associated with 28-day mortality. Conclusions: In this retrospective study, postoperative polymyxin B hemoperfusion did not show any survival benefit for the overall study population or any of the studied subgroups of patients with abdominal septic shock. A large multicentered prospective randomized trial is warranted to identify the true role of polymyxin B hemoperfusion in sepsis caused by Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

The benefit of endotoxin absorption therapy (direct hemoperfusion with polymyxin B-immobilized fiber: PMX-DHP) for severe septic patients is still controversial. There are limited data on the clinical experience and efficacy of PMX-DHP for septic patients with hematological disorders. At our institution, 16 patients with hematological diseases underwent PMX-DHP therapy for gram-negative septic shock from February 2006 to March 2012. Most of the patients had severe neutropenia (median neutrophil counts: 7/µL) due to intensive chemotherapy for their hematological diseases. After the PMX-DHP therapy, six patients recovered from the shock status (favorable group) and ten died of the sepsis (unfavorable group). We analyzed the differences between the two groups based on clinical characteristics just before PMX-DHP therapy. Regarding sequential organ failure assessment (SOFA) score, which is a scoring system to determine the degree of organ dysfunction, all patients in the favorable group scored less than 11. The sensitivity and specificity of SOFA score less than 11 for the therapeutic efficacy were 100% and 80%, respectively. Our results suggest that septic patients with hematological diseases may not be a candidate for PMX-DHP therapy when they have already developed serious organ dysfunction. [ABSTRACT FROM AUTHOR]

Sepsis is a major health problem and remains an important cause of death worldwide. The failure to convert advances in our understanding of the biologic features of sepsis into effective new therapies questions the current approach to the development of sepsis drugs, and suggests a need for newer and better clinical trial design. Blood purification for sepsis is a promising therapeutic strategy to improve survival and reduce organ failure in patients with severe sepsis and septic shock. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Sepsis caused by group B streptococcus has been well controlled with aminobenzylpenicillin, but the incidence of Escherichia coli sepsis has increased in proportion. E. coli is a Gram-negative bacillus associated with poor prognosis due to the release of endotoxins. Conventional treatment with antibiotics alone may not be sufficient because the inflammatory response exacerbates the unstable hemodynamic status. Polymyxin B hemoperfusion has been established as a treatment option for septic shock in adults. Polymyxin B hemoperfusion adsorbs endotoxins and cannabinoids such as anandamide and 2-arachidonoylglycerol. Reported herein is a case of severe septic shock induced by E. coli. The concomitant use of polymyxin B hemoperfusion rapidly reduced the requirement for catecholamines and the patient was discharged without short-term neurological or respiratory sequelae. It is suggested that polymyxin B hemoperfusion might be an innovative therapy for severe sepsis, and could improve outcome. [ABSTRACT FROM AUTHOR]

To investigate the relationship between survival and treatment-related reduction in endotoxin activity for patients in the Evaluating Use of PolymyxinB Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock trial with baseline endotoxin activity assay greater than or equal to 0.60 to less than 0.90 units., Design: Post hoc analysis of a multicenter randomized controlled clinical trial., Setting: Fifty-five tertiary hospitals in North America., Patients: Patients with septic shock and endotoxin activity assay level greater than or equal to 0.60 to less than 0.90 and multiple organ dysfunction syndrome greater than 9., Interventions: Two polymyxin B hemoperfusion treatments or Sham., Measurements and Main Results: One-hundred ninety-four patients were included (88 polymyxin B and 106 Sham). We evaluated the impact of changes in endotoxin activity assay based on comparison to the median reduction from baseline to day 3 and a second method where a target post-treatment endotoxin activity assay level (day 3) was established. The population median reduction in endotoxin activity assay level was 10.4%. In patients with a greater than median reduction, there was trend toward lower mortality with polymyxin B (17.1% vs 33.3%; p = 0.07) and a significant increase in mechanical ventilation-free days (20 vs 13.5; p = 0.04). The pressure adjusted heart rate showed a significant improvement in the polymyxin B group ( p = 0.02). For patients who achieved an endotoxin activity assay of less than 0.65 at day 3, the polymyxin B treated group had a trend toward a mortality reduction compared to Sham (16% vs 33%; p = 0.06) and a significant increase in ventilation-free day (20 vs 16; p = 0.05). Kaplan-Meier analysis showed a 17% reduction in mortality with polymyxin B ( p = 0.04)., Conclusions: These findings suggest that reducing endotoxin activity assay levels with polymyxin B as measured by comparison to a median reduction or when a treatment target is established, may result in improvements in mortality and organ function outcomes. This article is the first to report endotoxin activity assay measurements in response to polymyxin B use versus Sham in patients with septic shock and elevated endotoxin activity assay. These findings are considered to be hypothesis generating and will need to be prospectively validated., Competing Interests: Dr. Rachoin discloses that he received consultant’s fees and travel expenses from Spectral Medical. Foster discloses that she is an employee of Spectral Medical and her spouse is also an employee of Spectral Medical. Giese received consultant’s fees and travel expenses payments from Spectral Medical and owns stocks in the company. Dr. Weisberg discloses that he received consultant’s fees from Spectral Medical and PLC medical systems. Dr. Klein discloses that he received consultant’s fees from Spectral Medical. The authors declare that the polymyxin B therapy is being studied under Investigational Device Exemption G090151 and is not approved at present by U.S. Food and Drug Administration., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.Methods: We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.Results: Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.Conclusion: PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.Trial Registration: ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015. [ABSTRACT FROM AUTHOR]

Background: Descending necrotizing mediastinitis is a common and progressive polymicrobial infection involving the neck and chest with a high death rate (10 to 40%). From a microbiological point of view, descending necrotizing mediastinitis is sustained by Gram-positive bacteria (43-62%), anaerobes (46-78%), and, rarely, Gram-negative bacteria. Data collected during the Antibiotic Resistance-Istituto Superiore di Sanità project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance. In particular, 32.9% of Klebsiella pneumoniae isolates were resistant to carbapenem, 33.6% of Staphylococcus aureus to methicillin, and 28.7% and 43.9% of Escherichia coli isolates to third-generation cephalosporins and fluoroquinolones, respectively.Case Presentation: We describe the case of a 38-year-old white man with septic shock due to descending necrotizing mediastinitis sustained by multidrug-resistant Gram-negative and Gram-positive bacteria treated after surgery with an IgM-enriched immunoglobulin preparation and polymyxin B hemoperfusion therapy.Conclusion: Despite the contrasting data on the use of immunoglobulins and polymyxin B hemoperfusion in septic shock and the lack of literature in cases of acute mediastinitis caused by both Gram-negative and Gram-positive multidrug-resistant bacteria, we obtained an improvement in clinical conditions and the survival of our patient, against all odds. [ABSTRACT FROM AUTHOR]

Purpose: We designed this study to examine the clinical effects of polymyxin B hemoperfusion (PMX-HP) in septic shock patients., Material and Methods: We retrospectively examined the effects of PMX-HP in septic shock patients with intra-abdominal or gram-negative bacterial infection during October 2013-May 2016. A one-to-one matching between the PMX-HP and conventional groups was performed, and 28-day mortality, and change in inotropic score, Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24h in the two groups were compared. In addition, multivariable regression analysis and Cox proportional hazards regression model were applied in all eligible patients., Results: Sixty-nine patients were eligible, of whom fifty patients were enrolled for matched cohort analysis. In matched cohort analysis, change in inotropic score after 24h (-24.8 [19.7] vs. -6.4 [20.0], p=0.002) differed significantly between the PMX-HP and conventional groups. Multivariable regression analysis revealed that PMX-HP was associated with lower 28-day mortality (odds ratio 0.18, 95% CI 0.04-0.92, p=0.039) and greater improvement in inotropic and APACHE II scores., Conclusions: PMX-HP may have potential benefits for hemodynamic and prognostic outcomes in septic shock patients with intra-abdominal or gram-negative bacterial infection., (Copyright © 2017. Published by Elsevier Inc.)