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.

Early Empirical Anidulafungin Reduces the Prevalence of Invasive Candidiasis in Critically Ill Patients: A Case-control Study.

Introduction: Invasive candidiasis (IC) in critically ill patients is a serious infection with high rate of mortality. As an empirical therapy, like antibiotics, the use of antifungals is not common in intensive care units (ICUs) worldwide. The empirical use of echinocandins including anidulafungin is a recent trend. Aim of the study: The objective of this study was to assess the impact of empirical anidulafungin in the development of invasive candidiasis in critically ill patients in ICU. Methods: This retrospective case-control study was conducted on 149 patients with sepsis with/without septic shock and bacterial pneumonia. All the patients were divided into two groups. The 'control group' termed as 'NEAT group' received no empirical anidulafungin therapy and the 'treated group' termed as 'EAT group' received empirical anidulafungin therapy in early hospitalization hours. Results: Seventy-two and 77 patients were divided into the control and the treated group, respectively. Patients in EAT group showed less incidences of IC (5.19%) than that of the NEAT group (29.17%) (p = 0.001). Here, the relative risk (RR) was 0.175 (95% CI, 0.064-0.493) and the risk difference (RD) rate was 24% (95% CI, 12.36%-35.58%). The 30-day all-cause mortality rate in NEAT group was higher (19.44%) than that of in EAT group (10.39%) (p = 0.04). Within the first 10-ICU-day, patients in the EAT group left ICU in higher rate (62.34%) than that in the NEAT group (54.17%). Conclusion: Early empirical anidulafungin within 6 h of ICU admission reduced the risk of invasive candidiasis, 30-day all-cause mortality rate and increased ICU leaving rate within 10-day of ICU admission in critically ill patients.

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.

Intravenous N-acetylcysteine in severe cutaneous drug reaction treatment: A case series.

Drug-induced serious adverse reaction is an unpleasant event with high rate of mortality. Stevens-Johnson Syndrome and toxic epidermal necrolysis are most common among the serious adverse drug reactions. There is no selective drug therapy for the management of serious adverse drug reactions-associated mucocutaneous blisters. The use of N-acetylcysteine in the treatment of mucocutaneous blisters has limited evidence worldwide. Three cases of toxic epidermal necrolysis or Stevens-Johnson Syndrome-associated mucocutaneous blisters are presented in this study where intravenous N-acetylcysteine (600 mg, every 8 h) was given in early hospitalization hours for the treatment of mucocutaneous fluid-filled blisters. Here, one patient with toxic epidermal necrolysis received intravenous immunoglobulin along with intravenous N-acetylcysteine and the other two patients (toxic epidermal necrolysis/Stevens-Johnson Syndrome) received only N-acetylcysteine intravenously. In response, mucocutaneous fluid-filled blisters stopped progressing within 48 h and were healed within 2 weeks of admission in the intensive care unit. Thus, intravenous N-acetylcysteine with or without having intravenous immunoglobulin in the treatment of serious adverse drug reactions-associated mucocutaneous blisters may be an effective therapeutic option for better clinical outcome.

Extensive Pneumocephalus Caused by Multidrug-Resistant Klebsiella pneumoniae.

Pneumocephalus is a life-threatening event associated with different infectious diseases and trauma. Klebsiella pneumoniae is a gas-forming organism that can cause pneumocephalus. A woman aged 56 years presented with a history of septic shock and community-acquired pneumonia. She was supported by mechanical ventilation in intensive care unit. Multidrug-resistant K. pneumoniae was detected in her blood and tracheal aspirate. Her level of consciousness reduced, and clinical condition was deteriorating. The computed tomography scan of the brain revealed abundant pneumocephalus entities. Multidrug-resistant K. pneumoniae was found in her cerebrospinal fluid while on appropriate antibiotic therapy. She died from acute stroke during her treatment.

High-voltage electrocution-induced pulmonary injury and cerebellar hemorrhage with fractures in atlas.

BACKGROUND: Electrocution is a common cause of mild to severe multisystem injuries leading to high rate of mortality and morbidity. Low to high-voltage injury may be clinically manifested from a simple unpleasant sensation to multiple soft tissue injury which may cause instant death. The severity of injury depends on intensity of the electrical current, voltage of the source, resistance in the victims' body and the duration of the contact. CASE PRESENTATION: A 20-year-old young male experienced with an accidental high-voltage electrocution injury from a blasted electrical transformer while passing across the road. He lost his consciousness and immediately hospitalized. Bilateral pulmonary infiltrates and right cerebellar hemorrhage with fractures in anterior and posterior arch of the first cervical vertebrae (C1) were diagnosed, and there was no history of electrical burn. He stayed in hospital for three days and completely treated with initial oxygen supplementation and immobilization of his head and neck with a Philadelphia collar for 6 weeks. Electrocution is a serious public health concern and reported worldwide with few fatal ending. Accidental high-voltage electrocution injury is a serious type of unfortunate accidental injuries which in most of times, ends with immediate or delayed sequelae or even death. In this case, the victim with high-voltage-associated electrical injuries in his lungs and brain was completely recovered because of early hospitalization. CONCLUSIONS: Electrocution injury is an accidental event with high mortality and morbidity rate. Mild to severe electrical current-induced injuries including burn can be treated successfully in most of the cases, but early hospitalization is highly required.

Bloodstream infection with pandrug-resistant Alcaligenes faecalis treated with double-dose of tigecycline.

INTRODUCTION: Alcaligenes faecalis is a species of gram-negative, rod-shaped, aerobic bacteria commonly found in the environment. A. faecalis-associated nosocomial infections are common in hospitalized patients, but serious life threatening infections are rare. Here, we report a rare case of BSI with A. faecalis resistant to all available antibiotics; successfully treated with double-dose of tigecycline. PRESENTATION OF CASE: A 60-year-old female presented with A. faecalis bloodstream infection, where the organism was completely resistant to all commercially available antibiotics including polymyxins and tigecycline. The physical condition of the patient was deteriorating and there were no active antibiotics available to prescribe based on sensitivities. Despite the organism's resistance to tigecycline, double-dose of tigecycline therapy (100 mg twice daily, intravenously after a 200 mg single intravenous loading dose) was prescribed intentionally for the treatment of this infection. The organism was completely eradicated from the bloodstream of that patient within the 5 days of therapy-initiation. DISCUSSION: Double-dose of tigecycline maintains a higher serum drug concentration rather than the standard dose, and in this case, double-dose of tigecycline completely cleared the pandrug-resistant A. faecalis from the blood where initially, that organism was resistant to tigecycline. Previously, A. faecalis isolates were found resistant to fluoroquinolones, but here it was found very rarely resistant to even reserve antibiotics, polymyxins, carbapenems and tigecycline. CONCLUSION: Pandrug-resistant A. faecalis-associated bloodstream infection is a very uncommon case and double-dose of tigecycline may be an effective option to treat it.

Donepezil: an unusual therapy for acute diphenhydramine overdose.

An elderly man presented with the history of diphenhydramine hydrochloride overdose as a suicidal attempt. At presentation, he was in an acute confusional state with several anticholinergic features and had to be managed in intensive care unit. As an antidote for diphenhydramine hydrochloride, donepezil was used instead of physostigmine due to the unavailability of physostigmine in Bangladesh. The patient improved within the next 24 hours; his level of consciousness improved and the anticholinergic features regressed.

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.