Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.
We present a method for identifying biomarkers in human lung injury. The method is based on highresolution nuclear magnetic resonance (NMR) spectroscopy applied to bronchoalveolar lavage fluid (BALF) collected from lungs of critically ill patients. This biological fluid can be obtained by bronchoscopic and non-bronchoscopic methods. The type of lung injury in acute respiratory failure presenting as acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), continues to challenge critical care physicians. We characterize different metabolites in BAL fluid by non-bronchoscopic method (mBALF) for better diagnosis and understanding of ALI/ ARDS by NMR spectroscopy. NMR spectra of mBALF collected from 30 patients (9 controls, 10 ARDS and 11 ALI) were analyzed for the identification of biomarkers. Statistical methods such as principal components analysis and partial least square discriminant analysis were carried out on 1 H NMR spectrum of mBALF to identify biomarker responsible for separation among different lung injuries classes (ALI and ARDS) and normal lungs. The corresponding correlation of biomarkers with metabolic cycle has given insight into metabolism of lung injuries in critically ill patients. Our study shows statistically significant differentiation of various metabolites concentration in mBALF collected from lungs of ALI, ARDS and healthy control patients, making NMR spectroscopy as a possible new method of characterizing human lung injury. Keywords Metabonomics Á PCA Á PLS-DA Á Bronchoalveolar lavage fluid (BALF) Á NMR spectroscopy Á Metabolic profiling Abbreviations BALF Bronchoalveolar lavage fluid mBALF Mini bronchoalveolar lavage fluid PCA Principal component analysis PLS-DA Partial least square discriminant analysis Electronic supplementary material The online version of this article (
We describe successful usage of low dose Tissue plasminogen activator (tPA) (30-50 mg) in three COVID19 critically ill patients, who were in worsening respiratory failure in-spite of being on therapeutic anticoagulation. All patients had respiratory rate > 40; FiO 2 > 0.7(on NIV); PiO 2 /FiO 2 ratio < 100 and D-dimer>1000 ng/ml. C.T. Pulmonary Angiography could not be done in these patients due to poor general condition, but 2D echo was normal and none of the patients was in shock. So there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we saw dramatic changes in oxygenation. All patients became off oxygen within 3-7 days and were discharged within 2 weeks. The whole idea was to prevent intubation, since mortality rates are very high in intubated COVID19 patients. tPA is associated with <1% risk of fatal bleed. In this unprecedented pandemic with high mortality rates, thrombolysis could be an effective and safe option in carefully selected critically ill patients of COVID19. Keywords Thrombolysis • COVID19 • Acute respiratory distress syndrome (ARDS) • Coagulopathy • Tissue plasminogen activator (tPA) Highlights• COVID19 related coagulopathy can cause extensive pulmonary micro thrombosis leading to ARDS and is one of the most important reasons for mortality. • We report three cases of COVID-19 disease who were in severe ARDS (PiO 2 /FiO 2 ratio < 100) and were on the verge of intubation. • Although no evidence of PTE was present on 2D echo, thrombolysis was done with low dose tPA; all patients had significant improvement and became off oxygen within 3-7 days.• Thrombolysis could be an effective and safe option in carefully selected critically ill patients of COVID19 ARDS and can prevent mortality.
Targeted temperature management (TTM) in today's modern era, especially in intensive care units represents a promising multifaceted therapy for a variety of conditions. Though hypothermia is being used since Hippocratic era, the renewed interest of late has been since early 21st century. There have been multiple advancements in this field and varieties of cooling devices are available at present. TTM requires careful titration of its depth, duration and rewarming as it is associated with side-effects. The purpose of this review is to find out the best evidence-based clinical practice criteria of therapeutic hypothermia in critical care settings. TTM is an unique therapeutic modality for salvaging neurological tissue viability in critically ill patients viz. Post-cardiac arrest, traumatic brain injury (TBI), meningitis, acute liver failure and stroke. TTM is standard of care in post-cardiac arrest situations; there has been a lot of controversy of late regarding temperature ranges to be used for the same. In patients with TBI, it reduces intracranial pressure, but has not shown any favorable neurologic outcome. Hypothermia is generally accepted treatment for hypoxic ischemic encephalopathy in newborns. The current available technology to induce and maintain hypothermia allows for precise temperature control. Future studies should focus on optimizing hypothermic treatment to full benefit of our patients and its application in other clinical scenarios.
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