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Adequate colistin exposure is important for microbiological clearance. This study was performed in critically ill patients18 years old to develop a simplified nonparametric pharmacokinetic (PK) model of colistin for routine clinical use and to determine the role of dose optimization. The Non-Parametric Adaptive Grid algorithm within the Pmetrics software package for R was used to develop a PK model from 47 patients, and external validation of the final model was performed in 13 patients. A 1-compartment multiplicative gamma error model with 0-order input and first-order elimination of colistin was developed with creatinine clearance and serum albumin as covariates on elimination rate constant. An R

Severe hypoxemic respiratory failure is frequently managed with invasive mechanical ventilation with or without prone position (PP). We describe 13 cases of nonhypercapnic acute hypoxemic respiratory failure (AHRF) of varied etiology, who were treated successfully in PP without the need for intubation. Noninvasive ventilation (NIV), high-flow oxygen via nasal cannula, supplementary oxygen with venturi face mask, or nasal cannula were used variedly in these patients. Mechanical ventilatory support is offered to patients with AHRF when other methods, such as NIV and oxygen via high-flow nasal cannula, fail. Invasive mechanical ventilation is fraught with complications which could be immediate, ranging from worsening of hypoxemia, worsening hemodynamics, loss of airway, and even death. Late complications could be ventilator-associated pneumonia, biotrauma, tracheal stenosis, etc. Prone position is known to improve oxygenation and outcome in adult respiratory distress syndrome. We postulated that positioning an unintubated patient with AHRF in PP will improve oxygenation and avoid the need for invasive mechanical ventilation and thereby its complications. Here, we describe a series of 13 patients with hypoxemic respiratory of varied etiology, who were successfully treated in the PP without endotracheal intubation. Two patients (15.4%) had mild, nine (69.2%) had moderate, and two (15.4%) had severe hypoxemia. Oxygenation as assessed by PaO2/FiO2 ratio in supine position was 154 ± 52, which improved to 328 ± 65 after PP. Alveolar to arterial (A-a) O2 gradient improved from a median of 170.5 mm Hg interquartile range (IQR) (127.8, 309.7) in supine position to 49.1 mm Hg IQR (45.0, 56.6) after PP. This improvement in oxygenation took a median of 46 hours, IQR (24, 109). Thus, voluntary PP maneuver improved oxygenation and avoided endotracheal intubation in a select group of patients with hypoxemic respiratory failure. This maneuver may be relevant in the ongoing novel coronavirus disease pandemic by potentially reducing endotracheal intubation and the need for ventilator and therefore better utilization of critical care services. How to cite this article Rao SV, Udhayachandar R, Rao VB, Raju NA, Nesaraj JJJ, Kandasamy S, et al. Voluntary Prone Position for Acute Hypoxemic Respiratory Failure in Unintubated Patients. Indian J Crit Care Med 2020;24(7):557–562.

Staphylococcus aureus is of significant clinical concern in both community- and hospital-onset infections. The key to the success of S. aureus as a pathogen is its ability to swiftly develop antimicrobial resistance. Methicillin-resistant S. aureus (MRSA) is not only resistant to nearly all beta-lactams but also demonstrates resistance to several classes of antibiotics. A high prevalence of MRSA is seen across worldwide. For many decades, vancomycin remained as gold standard antibiotic for the treatment of MRSA infections. In the past decades, linezolid, daptomycin, ceftaroline and telavancin received regulatory approval for the treatment of infections caused by resistant Gram-positive pathogens. Although these drugs may offer some advantages over vancomycin, they also have significant limitations. These includes vancomycin's slow bactericidal activity, poor lung penetration and nephrotxicity;linezolid therapy induced myelosuppression and high cost of daptomycin greatly limits their clinical use. Moreover, daptomycin also gets inactivated by lung naturally occurring surfactants. Thus, currently available therapeutic options are unable to provide safe and efficacious treatment for those patients suffering from hospital-acquired pneumonia, bloodstream infections (BSIs), bone and joint infections and diabetic foot infections (DFI). An unmet need also exists for a safe and efficacious oral option for switch-over convenience and community treatment. Herein, the review is intended to describe the supporting role of anti-staphylococcal antibiotics used in the management of S. aureus infections with a special reference to levonadifloxacin. Levonadifloxacin and its prodrug alalevonadifloxacin are novel benzoquinolizine subclass of quinolone with broad-spectrum of anti-MRSA activity. It has been recently approved for the treatment of complicated skin and soft-tissue infection as well as concurrent bacteraemia and DFI in India.

Background and Aims: Tissue hypoperfusion is reflected by metabolic parameters such as lactate, central venous oxygen saturation (ScvO 2 ) and the veno-arterial CO 2 (vaCO 2 ) difference. We studied the relation of these parameters over time and with outcome in patients with severe septic shock. Materials and Methods: In this single-center, prospective observational cohort study, adult patients (≥18 years) with circulatory shock were included. Echocardiography and simultaneous arterial and venous blood gases were done on enrolment (0 h) and at 24, 48 and 72 h. The partial pressure of CO 2 , lactate and ScvO 2 were recorded from the central venous blood samples. The vaCO 2 was calculated as the difference in CO 2 between paired venous and arterial blood gas samples. Results: Of the 104 patients with circulatory shock, 79 patients (44 males) with septic shock aged 49.8 (standard deviation ± 14.6) years and with sequential organ failure assessment (SOFA) score of 11.0 ± 3.4 were included. 71 patients (89.9%) were ventilated (11.4 ± 12.3 ventilator-free days). The duration of hospitalization was 16.6 ± 12.8 days and hospital mortality 50.6%. Lactate significantly decreased over time with a greater decrement in survivors than nonsurvivors (−0.35 vs. −0.10, P 2 decreased by 0.34 mmHg ( P = 0.006). There was no association between ScvO 2 and mortality ( P = 0.930). 0 h SOFA and vaCO 2 ≤6 mmHg were strongly associated ( P = 0.005, P = 0.018, respectively) with higher odds of mortality. However, this association was evident only in those with ScvO 2 >70% and not in ScvO 2 ≤70%. Conclusion: In septic shock, vaCO 2 ≤6 mmHg is independently associated with mortality, particularly in those with normalized ScvO 2 consistent with metabolic microcirculatory abnormalities in these patients.

Bleeding complications of dengue hemorrhagic fever such as epistaxis, gum bleeding, gastrointestinal bleeding, hypermenorrhea, hematuria, and thrombocytopenia have been documented. A 49-year-old female presented with complaints of intermittent high-grade fever for the past 4 days, lower abdominal pain and altered sensorium for 1 day. Laboratory investigations revealed severe anemia, mild thrombocytopenia, hypofibrinogenemia, and positive dengue serology. Emergency ultrasound examination of the abdomen revealed a possible rapidly expanding hematoma from the inferior epigastric artery and suggested urgent computed tomography (CT) angiogram for confirmation of the same. CT angiogram was confirmatory, and patient underwent emergency embolization of the right inferior epigastric artery. We report the first case of inferior epigastric hemorrhage and rectus sheath hematoma as a consequence of dengue.

Background: A. baumannii-calcoaceticus (Abc) complex has surfaced as a major nosocomial pathogen causing blood stream infection and ventilators associated pneumonia (VAP). Carbapenems have come to be the cornerstone of treatment for Abc complex. However, there has been an increased incidence of infections with carbapenem resistant strains. To validate the clinical practice of combination antibiotic therapy, in-vitro combinations of antibiotics have been examined using checkerboard methods, E-tests, and the reference, time-kill assay. Method: A prospective pilot study was conducted for the duration of one year. Twenty five isolates of carbapenem resistant Abc complex cultured from endotracheal aspirates of patients admitted in medical and surgical intensive care units diagnosed with ventilator associated pneumonia were collected. Isolates were tested for MIC (Minimum inhibitory concentration) by micro-broth dilution method for meropenem, sulbactam and colistin. Synergism between sulbactam plus meropenem and sulbactam plus colistin was tested by micro-broth checkerboard assay and the reference, time kill assay. Result: Minimum inhibitory concentration ranges (μg/ml) for sulbactam, meropenem, and colistin were 16-512, 16-256, and 0.5-64, respectively. MIC50 for sulbactam, meropenem, and colistin was 128, 128 and 1, correspondingly, and MIC90 for sulbactam, meropenem, and colistin was 256, 256 and 2, respectively. In the checkerboard assay and time-kill assay, a higher percentage of synergy was noted for the combination of sulbactam plus meropenem. Conclusion: Against multi-drug resistant (MDR) isolates of Abc complex, commendable synergy was seen with time kill assay for sulbactam plus meropenem combination. Therefore, in-vitro combinations of antimicrobial agents are most effective than the single agent against multidrug resistant organism.

Control of postpartum hemorrhage is difficult in patients with coagulopathy due to acute liver failure. Recombinant activated factor VII (rFVIIa) can help in control of bleed; however, it has short duration of action (2–4 h). The study aimed to report the use of rFVIIa in this setting. We retrospectively analyzed all patients with acute liver failure secondary to pregnancy-related liver disorders who received rFVIIa for control of postpartum hemorrhage (six patients, all six met diagnostic criteria for acute fatty liver of pregnancy). One dose of rFVIIa achieved adequate control of bleeding in five patients, while one patient needed a second dose. rFVIIa administration corrected coagulopathy and significantly reduced requirement of packed red cells and other blood products. No patient had thrombotic complications. In conclusion, rFVIIa was a useful adjunct to standard management in postpartum hemorrhage secondary to acute liver failure of pregnancy-related liver disorders.

The O 2 -CO 2 diagram is an often neglected but very useful tool to understand the implications of arterial blood gas (ABG) analysis, which is a challenging concept not only to the undergraduate medical student but also to practicing clinicians. Here, we present a simplified description of the O2-CO2 diagram that was developed in all its elegance by Rahn and Fenn (6) and subsequently reviewed by others (2, 5). The O2-CO2 diagram plots PCO2 on the y-axis against PO2 on the x-axis. Any set of values of PO2 and PCO2, whether in atmospheric air, tracheal (inspired) air, alveolar air, mixed expired air, arterial blood, or venous blood, can be plotted on this diagram. It will be appreciated at the end of this discussion that 1) there are certain physical limits to what combinations of O2 and CO2 can exist in the alveolus and, therefore, the blood; and 2) even if arterial blood gases are the only available laboratory parameters, one can make reasonable assumptions about alveolar gas composition and assess if a patient has a pure ventilatory defect or a diffusion defect; however, it is difficult to assess mixed disorders without direct measurement of alveolar gas partial pressures. To begin, let us review the composition of atmospheric air, inspired air, and alveolar air (Fig. 1). Dry atmospheric air is composed of 21% O 2, with the rest N2 and negligible CO2. Therefore, PO2 in dry atmospheric air at sea level is 21% of the atmospheric pressure (Patm) of 760 mmHg, which is 159 mmHg. As air passes through the upper airways during inspiration, it is saturated with water vapor, the partial pressure of which at body temperature, pressure, saturated (BTPS) is 47 mmHg. The addition of water vapor dilutes inspired air, thereby reducing both the partial pressure of nitrogen and PO2 proportionally. The PO2 in inspired air is therefore 149 mmHg [21% of (760 47) mmHg] and is henceforth represented as PIO2 . While the inspired air in the conducting zone is composed of N2 ,O 2, and water vapor, a fourth gas, namely, CO2, is added to alveolar air. Since the alveoli are open to the atmosphere and during either phase of respiration alveolar pressure is only slightly different from Patm, it is safe to assume that alveolar pressure at all times is almost equal to Patm or the total pressure of inspired air (760 mmHg). The partial pressures of nitrogen (564 mmHg) and water vapor (47 mmHg) are almost the same in inspired and alveolar air. The remaining 149-mmHg pressure is due to O 2 alone in the inspired air (PI O2 ), whereas in the alveolus, the combined pressures of O 2 (PA O2 ) and CO 2 (PA CO2 ) must be close (but not necessarily equal 1 ) to 149 mmHg. Since O 2 diffuses out of the alveolus, it is obvious that removal of O2 and, therefore, reduction of its partial pressure compensates for the addition of CO2. The crude relationship is therefore as follows

A case of Mycobacterium fortuitum bacteraemia in an immunocompromised patient confirmed by four positive serial blood cultures is reported here. The patient was a known case of acute lymphoblastic leukemia (ALL) on intensive chemotherapy. The source of bacteraemia was most probably a peripherally inserted vascular catheter. After initiation, of treatment with amikacin to which the strain was sensitive and clarithromycin and removal of the central line the patient′s fever defervesced and repeat blood cultures were negative. This is the first time we have encountered an immunocompromised patient with M. fortuitum septicaemia in our hospital. The possibility of an infection with rapidly growing mycobacteria is important to consider when conventional organisms are not isolated in culture especially in the context of patients with malignancy.

Zygomycosis is an infection due to the fungi Zygomycetes, which, despite being ubiquitous, rarely cause disease in humans. Predisposing conditions include diabetic ketoacidosis, hematologic malignancies, iron overload, multiorgan failure, chronic liver disease, renal failure, metabolic acidosis and immunosuppressed state [1–3]. Zygomycosis can rarely occur in pregnancy as a complication of diabetic ketoacidosis [1]. We report zygomycosis occurring in a non-diabetic woman with pregnancy—related liver disease and multi-organ failure. A 20-year-old woman presented to our center at 38 weeks of gestation (primigravida) with history of swelling of feet and fatigue for 10 days, breathlessness, and jaundice (3 days), and abdominal pain (1 day). She had no prior major illness. She had not taken any drug known to cause liver dysfunction. On presentation, she was conscious and oriented, her blood pressure was 140/90 mmHg, pulse rate was 124/min and respiratory rate was 36/min. She was icteric and pale. Abdominal examination showed a gravid uterus; there was no ascites or palpable mass. Urinalysis revealed proteinuria and pelvic ultrasound showed intrauterine death of the fetus. Her laboratory results were: hemoglobin 13 gm%, white cell count 12,800/cmm, platelet count 56,000/cmm, serum bilirubin 16.6 mg/dL, alanine transaminase 130 IU/L, creatinine 3.4 mg/dL, random blood sugar 160 mg/dL, lactate dehydrogenase 892 IU/L, and INR 4.2. Arterial blood gas analysis showed pH 7.2, lactate 7.3 mmol/L, anion gap 12.6 and, base excess −17.5. Etiological work up for liver dysfunction like peripheral smear for malaria and serology for hepatitis viruses (hepatitis A, B, C and E) was non-contributory. Her blood culture was sterile. A diagnosis of pregnancy—related liver dysfunction [Diagnostic criteria for acute fatty liver of pregnancy (AFLP) and pre-eclamptic liver dysfunction and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome were met] with intra-uterine death was made. She was started on piperacillin with tazobactam and metronidazole intravenously. After a failed attempt to induce vaginal delivery, she underwent emergency cesarean section under blood product coverage 22 h after admission to our hospital. The baby delivered was a macerated stillbirth. There was 750 mL of ascites drained and 500 mL of blood loss during the surgery. She was maintained on the same antibiotics in intensive care unit and was on mechanical ventilation with other supportive measures. Hemodialysis was instituted, with which acidosis resolved partially (pH 7.35), but she had persistent lactic acidemia (lactate >4 mmol/L) with worsening liver functions and recurrent hypoglycemia. A. Goel (*) :U. Zachariah : C. E. Eapen Department of GI Sciences, Christian Medical College, Vellore 632 004, India e-mail: drashish_goel@yahoo.com