Aerosolized Plus Intravenous Polymyxin B Versus Colistin in the Treatment of Pandrug-Resistant Klebsiella Pneumonia-mediated Ventilator-Associated Pneumonia: A Retrospective Cohort Study in Bangladesh.

Background: Pandrug-resistant Klebsiella pneumoniae ventilator associated pneumonia (VAP) is associated with high rate of mortality in intensive care unit (ICU) and has been recognized as a difficult-to-treat infection worldwide. Polymyxin B or colistin-based combination therapies are frequently used worldwide though microbial eradication rate is not promising. Aim: The aim of this study is to compare the clinical outcome of intravenous with aerosolized polymyxin B versus colistin in the treatment of pandrug-resistant K. pneumoniae VAP. Methods: This retrospective cohort study was conducted on 222 mechanically ventilated patients admitted from May 11, 2019 to October 19, 2020. K. pneumoniae isolates were resistant to all available antibiotics, including polymyxins in culture sensitivity tests. As treatment, polymyxin B and colistin was administered in intravenous and aerosolized form concurrently twice daily in 106 patients and 116 patients in PMB and CLN group, respectively for 14 days. Survival rate, safety, and clinical outcomes were compared among the groups. The Cox proportional-hazard model was performed to calculate hazard ratio (HR) with 95% confidence intervals (CI). Results: Patients in PMB group showed more microbial eradication than the patients CLN group [68.1% (n=116)/83% (n=106), respectively; P <0.05). The median day of intubation and ICU stay in PMB group was shorter than that in CLN group [10 (IQR: 9-12.25) vs. 14 (IQR: 11-19), P <0.05; 12 (IQR: 10-14) vs. 15 (IQR: 9-18.5), P=0.072, respectively] with reduced 60-day all-cause mortality rate [15% (n=106) vs. 21.55% (n=116)]. Polymyxin B improved survival compared to colistin (multivariate HR: 0.662; 95% CI=0.359-1.222, P=0.195). Conclusions: Concurrent administration of intravenous and aerosolized polymyxin B in patients with pandrug-resistant K. pneumoniae-associated VAP revealed better microbial eradication, reduced the length of intubation and ICU stay, and improved survival rate compared to colistin.

Therapeutic safety and efficacy of triple-immunosuppressants versus dual-immunosuppressants in severe-to-critical COVID-19: a prospective cohort study in Bangladesh.

BACKGROUND: Hyperinflammation-induced respiratory failure is a leading cause of mortality in COVID-19 infection. Immunosuppressants such as, Baricitinib and interleukin inhibitors are the drug-of-choice to suppress cytokine storm in COVID-19. Here, we compared the therapeutic safety and efficacy of triple-immunosuppressants with dual-immunosuppressants in patients with severe-to-critical COVID-19. METHODS: This study was conducted on 103 confirmed COVID-19 patients. Of 103 patients, 49 (N) and 54 (N) patients received dual-immunosuppressants (baricitinib plus two doses of secukinumab) and triple immunosuppressants (baricitinib plus single dose of tocilizumab and secukinumab) in group A and group B, respectively. Groups were compared in terms of clinical outcome, critical support-requirement, survival, re-hospitalisation, and adverse events (AEs). RESULTS: Patients in group B achieved normal blood oxygen saturation level (SpO2) earlier than the patients of group A [4 day (IQR: 3-12) vs 5 day (IQR: 5-14), p < .05]. The requirement of intensive care unit (ICU) and mechanical ventilation (MV) support was less in group B than group A [16.7%/28.6%, 11.1%/18.4%, respectively p < .05]]. The incidence of COVID-19 acute respiratory distress syndrome and 60-day all cause mortality was reduced in group B compared to group A [0.43 (0.19-0.98), p < .05; 0.35 (0.08-1.44), p > .05]. The 60-day re-hospitalisation rate was two-fold high in group A than group B (p = .024). Immunosuppressant-associated adverse events and secondary bacterial/fungal infections were relative high in patients of group B. CONCLUSIONS: Triple-immunosuppressants in severe-to-critical COVID-19 infection exhibited better clinical outcome; reduced ICU and MV requirement; shorter hospital stay with deceased 60-day all cause mortality and re-hospitalisation compared to dual-immunosuppressants.

The Susceptibility of MDR-K. Pneumoniae To Polymyxin B Plus Its Nebulised Form Versus Polymyxin B Alone in Critically Ill South Asian Patients.

INTRODUCTION: Critically ill patients in intensive care units are at high risk of dying not only from the severity of their illness but also from secondary causes such as hospital-acquired infections. USA national medical record-data show that approximately 10% of patients on mechanical ventilation in an intensive care unit developed ventilator-associated pneumonia. Polymyxin B has been used intravenously in the treatment of multi-drug resistant gram-negative infections, either as a monotherapy or with other potentially effective antibiotics, and the recent international guidelines have emphasised the use of nebulised polymyxin B together with intravenous polymyxin B to gain the optimum clinical outcome in ventilator-associated pneumonia cases caused by multi-drug resistant gram-negative infections. METHODS: One hundred and seventy-eight patients with ventilator-associated pneumonia due to multi-drug resistant K. pneumoniae were identified during the study period. Following the inclusion and exclusion criteria, 121 patients were enrolled in the study and randomly allocated to two study groups. Group 1 patients were treated with intravenous Polymyxin B plus nebulised polymyxin B (n=64) and Group 2 patients with intravenous Polymyxin B alone (n=57). The study aimed to compare the use of Polymyxin B plus its nebulised form to polymyxin B alone, in the treatment of MDR-K. pneumoniae associated ventilator-associated pneumonia in critically ill patients. RESULTS: In Group 1, a complete clearance of K. pneumoniae was found in fifty-nine patients (92.1%; n=64) compared to forty patients (70.1%, n=57) in the Group 2 (P<0.003). The average time till extubation was significantly higher in Group 2 compared to Group 1 (P<0.05). The total length-of-stay in the ICU was significantly higher in Group 2 compared to Group 1. (P<0.05). These results support the view that the Polymyxin B dual-route regime may be considered as an appropriate antibiotic therapy, in critically ill South Asian patients with ventilator-associated pneumonia.

Impact of high dose of baricitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh.

PURPOSE: Hyperinflammation in severe COVID-19 infection increases the risk of respiratory failure and one of the cogent reasons of mortality associated with COVID-19. Baricitinib, a janus kinases inhibitor, can potentially suppress inflammatory cascades in severe COVID-19 pneumonia. METHODS: The objective of this study was to compare the clinical outcomes of high dose of baricitinib with its usual dose in patients with severe COVID-19 pneumonia. This prospective cohort study was conducted on 238 adult patients with severe COVID-19 pneumonia. Eight milligram and 4 mg of baricitinib was given orally to 122 patients in the high dose (HD) group and 116 patients the usual dose (UD) group, respectively daily for 14 days, and clinical outcomes were compared among the groups. RESULTS: Blood oxygen saturation level was stabilized (≥94% on room air) earlier in the HD group compared to the UD group [5 (IQR: 4-5)/8 (IQR: 6-9), P < 0.05]. Patients in the HD group required intensive care unit (ICU) and intubation supports more in the UD group than that in patients of the HD group [17.2%/9%, P < 0.05; 11.2%/4.1%, P > 0.05; N = 116/122, respectively]. The 30-day mortality and 60-day rehospitalization rate were higher in the UD group than the HD group [6%/3.3%, P < 0.01; 11.9%/7.6%, P > 0.05; N = 116/122, respectively]. CONCLUSION: The daily high dose of baricitinib in severe COVID-19 results in early stabilization of the respiratory functions, declined requirements of critical care supports, reduced rehospitalization with mortality rate compared to its daily usual dose.

Additional baricitinib loading dose improves clinical outcome in COVID-19.

Pneumonia associated with coronavirus disease 2019 (COVID-19) has been accounted for high mortality rate in severe COVID-19 worldwide, and additional serious scarcity of standard and effective anti-inflammatory drug in COVID-19 pneumonia management is a big challenge. Baricitinib, a Janus kinase (JAK) inhibitor, is a promising drug in COVID-19 pneumonia. This study aims to compare the clinical outcome of moderate-to-severe COVID-19 pneumonia treated with baricitinib with or without a loading dose. This prospective case-control study enrolled 37 adult patients where 17 patients (control) received baricitinib at 4 mg oral daily dose and 20 patients (case) received an additional single 8 mg oral loading dose. The median day to gain blood oxygen saturation level ≥95% (in room air) and return in normal breathing function were lower in case group than the control group. The requirement of intensive care unit and mechanical ventilation support was higher in the control group than in the case group [29.4% (N = 17)/10% (N = 20), P < 0.05; 11.8% (N = 17)/5% (N = 20), P > 0.05), respectively]. Thus, an additional loading dose of baricitinib revealed better clinical outcome of patients with COVID-19 pneumonia.

A young adult with post-traumatic breathlessness, unconsciousness and rash.

Can you diagnose this young adult with post-traumatic breathlessness, unconsciousness and rash? http://bit.ly/2LlpkiV.

The Use of High Dose Eltrombopag in the Management of Sepsis-Associated Thrombocytopenia in Critically Ill Patients.

INTRODUCTION: Sepsis is a life-threatening condition, and sepsis-associated thrombocytopenia (SAT) is a common consequence of the disease where platelet count falls drastically within a very short time. Multiple key factors may cause platelet over-activation, destruction and reduction in platelet production during the sepsis. Eltrombopag is a thrombopoietin receptor agonist and is the second-line drug of choice in the treatment of chronic immune thrombocytopenia (ITP). AIM OF THE STUDY: The objective of this study was to observe the therapeutic outcome of high dose eltrombopag in SAT management in critically ill patients. MATERIAL AND METHODS: This 6-month-long single group, observational study was conducted on seventeen ICU patients with SAT. Eltrombopag 100 mg/day in two divided doses was given to each patient. Platelet counts were monitored. A low platelet blood count returning to 150 K/µL or above, is taken as indicative of a successful reversal of a thrombocytopenia event. RESULTS: The mean Apache II score of patients (n= 17) was 18.71 (p-value: >0.05). No eltrombopag-induced adverse event was observed among the patients during the study period. Thrombocytopenia events were reversed successfully in 64.71% of patients (11; n= 17) within eight days of eltrombopag therapy. CONCLUSIONS: The therapeutic potentiality of high dose eltrombopag regime in the management of sepsis-associated thrombocytopenia was found clinically significant in over two-thirds of critically ill adult patients enrolled in the study. These data may point to a new strategy in the management of acute type of thrombocytopenia in septic patients.