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Mediterranean spotted fever (MSF) is a tick-borne acute endemic infectious disease caused by Rickettsia conorii. While MSF may progress asymptomatically, it may lead to clinical pictures like severe hemorrhagic fever. In this article, we are presenting an MSF case with signs of high fever, headache, nausea, weakness and generalized maculopapular rash. The diagnosis of the female patient who had a history of contact with a tick-infested dog was confirmed with her clinical and laboratory data. The clinical and laboratory findings of the patient who was given doxycycline by 200 mg/day for 7 days were improved in a short time. Rickettsia conorii serology by indirect immunofluorescence assay method confirmed the diagnosis of MSF. In cases of severe sepsis accompanied by high fever and generalized maculopapular rash where the source of the infection cannot be determined in the short term, carefully questioning exposure to ticks by considering the existing geographical, seasonal and endemic environmental factors may be life-saving in terms of early diagnosis and treatment of MSF, which may become fatal even in the absence of eschars (tache noire). The symptomatology of hemorrhagic fever associated with Rickettsia conorii may be confused with that of sepsis in clinical practice.

Background: Diagnoses recorded in administrative databases have limited utility for accurate identification of severe sepsis and disseminated intravascular coagulation (DIC). We evaluated the performance of alternative identification methods that use procedure records. Methods: We obtained data for adult patients admitted to intensive care units in three hospitals during a 1-year period. Severe sepsis and DIC were identified by three means: laboratory data, diagnoses, and procedures. Using laboratory data as a reference, the sensitivity and specificity of procedure-based methods and diagnosis-based methods were compared. Results: Of 595 intensive care unit admissions, 212 (35.6%) and 81 (13.6%) were identified as severe sepsis and DIC, respectively, using laboratory data. The sensitivity of procedure-based methods for identifying severe sepsis was 64.2%, and the specificity was 65.3%. Two diagnosis-based methods -the Angus and Martin algorithms- exhibited sensitivities of 21.7% and 14.6% and specificities of 98.7% and 99.5%, respectively, for severe sepsis. For DIC, the sensitivity of procedure-based methods was 55.6%, and the specificity was 67.1%, and the sensitivity and specificity of diagnosis-based methods were 35.8% and 98.2%, respectively. Conclusions: Procedure-based methods were more sensitive and less specific than diagnosis-based methods in identifying severe sepsis and DIC. Procedure records could improve disease identification in administrative databases.

Objective To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. Design A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Results Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pa o 2 /Fi o 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pa o 2 /F i o 2 <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Conclusions Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Objectives. To examine the impact of implementing sepsis bundle in multiple Asian countries, having 'team' vs. 'non-team' models of patient care. Design. Prospective cohort study. Setting. Eight urban hospitals, five countries in Asia. Participants. Adult patients with severe sepsis or septic shock. Interventions. Implementation was divided into six quartiles: Baseline, Education and four Quality Improvement quartiles. Main outcome measures. Quarterly bundle compliance and in-hospital mortality with respect to bundle completion and implementation model. Methods. In the team model, the implementation was championed by intensivists, where the bundle was completed in the intensive care unit. The non-team model led by emergency physicians completed the bundle in the emergency department as part of standard care. Results. Five hundred and fifty-six patients were enrolled. The overall in-hospital mortality rate was 29.9%, and 67.1% of the patients had septic shock. Compliance to the bundle was 13.3, 26.9, 37.5, 45.9, 48.8 and 54.5% over the six quartiles of implementation (P < 0.01). With team model, compliance increased from 37.5% baseline to 88.2% in the sixth quartile (P < 0.01), whereas hospitals with a non-team model increased compliance from 5.2 to 39.5% (P < 0.01). Crude in-hospital mortality was better in the patients who received the entire bundle (24.5 vs. 32.7%, P = 0.04). Bundle completion was associated with crude in-hospital mortality reduction (odds ratio 0.67, 95% confidence interval 0.45-0.99), but this survival benefit disappeared after adjustment for confounding variables. Conclusions. Through education and quality improvement efforts, initially low sepsis bundle compliance was improved in Asia. A team model was more effective in achieving bundle compliance compared with a non-team model.

Context: Rapid treatment of sepsis is of crucial importance for survival of patients. Specific and rapid markers of bacterial infection have been sought for early diagnosis of sepsis. One such measurement, Procalcitonin (PCT), has recently become of interest as a possible marker of the systemic inflammatory response to infection. Aims: This study was done to find out the common sources of sepsis and to evaluate the diagnostic value of PCT, its predictive value and its relation with Sepsis-related Organ Failure Assessment (SOFA) scores and mortality in various stages of sepsis. Settings and Design: The prospective study was conducted at our tertiary care center from October 2006 to December 2008. A total of 100 patients were included in the study. The study sample included all patients aged above 18 years presenting consecutively to our center during the study period with acute sepsis. They were divided into three groups: sepsis, severe sepsis and septic shock based on standardized criteria. Materials and Methods: PCT and various other relevant factors were measured in all study subjects. These parameters were compared among the three study groups. The statistical analyses were done using Student \"t\" test and two-way analysis of variance (ANOVA). Results: Respiratory tract infection was the most common source of sepsis. PCT proved to be an excellent indicator of sepsis with sensitivity of 94%. There was a significant association between serum PCT and SOFA scores (P < 0.05). Serum PCT levels did not predict mortality in the present study. Conclusions: PCT is among the most promising sepsis markers, capable of complementing clinical signs and routine lab parameters suggestive of severe infection.

Validation of compliance with severe sepsis bundles is still needed. The purpose of this study was to determine compliance and its outcomes in severe community-acquired pneumonia (CAP) patients in a limited resources country. A prospective cohort study of 212 severe CAP patients was carried out. The implementation programme was organized into two continuous phases. The primary outcomes were compliance and hospital mortality. Compliance with administration of antibiotics and vasopressors as well as plateau pressure on average < 30 cm H2O was high in both groups. In the bundles group, patients received more serum lactate monitoring (62.3% vs. 11.3%), more blood cultures (47.1% vs. 24.5%), more fluid resuscitation (63.2% vs. 26.4%) and volumes infused (1319.8 ±1107.4 ml vs. 461.9 ±799.3 ml), more inotropic dobutamine and/or packed red blood cells (21.7% vs. 10.0%), more low-dose steroids (56.5% vs. 15.0%), and more glucose control (51.9% vs. 6.6%) compared with such patients in the control group. The rates of total compliance with 6-hour, 24-hour, and 6/24-hour bundles in the prospective period were 47.1%, 51.9%, and 42.5%, respectively. Hospital mortality was reduced from 44.3% to 29.2% (p = 0.023) in the bundles group, and the compliant subgroup had a more than twofold decrease in mortality (17.8% vs. 37.7%, p = 0.003). Serum lactate measured, blood cultures, and fluid resuscitation showed independent relationships with decreased mortality. Total compliance was relatively low, but the implementation of severe sepsis bundles could clearly reduce mortality from severe CAP.

Background Epidemiologic data have shown an increasing incidence and declining mortality rate in sepsis. However, confounding effects due to differences in disease classification might have contributed to these trends. To assess if a declining mortality over time could be supported by data derived from high-quality prospective studies, we performed a meta-analysis using data from randomised controlled trials (RCTs) on sepsis. The primary aim was to assess whether the mortality in sepsis trials has changed over time. The secondary aim was to investigate how many of the included trials could show efficacy of the studied intervention regarding 28-day mortality. Methods We searched PubMed for RCTs enrolling patients with severe sepsis and septic shock, published between 2002 and 2016. The included trials were assessed for quality and sorted by date of first inclusion. A meta-analysis was performed to synthesise data from the individual sepsis trials. Results Of 418 eligible articles, 44 RCTs on sepsis were included in the analysis, enrolling 13,315 patients in the usual care arm between 1991 and 2013. In this time period, mortality decreased by 0.42% annually ( p  = 0.04) to give a total decline of 9.24%. In subgroup analyses with adjustments for APACHE II, SAPS II and SOFA scores, the observed time trend was not significant ( p  = 0.45, 0.23 and 0.98 respectively). Only four of the included trials showed any efficacy with regard to mortality. Conclusions Data from RCTs show a declining trend in 28-day mortality in severe sepsis and septic shock patients during the years from 1991 to 2013. However, when controlling for severity at study inclusion, there was no significant change in mortality over time. The number of trials presenting new treatment options was low. Trial registration PROSPERO CRD42018091100 . Registered 27 August 2018.

Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [ 1 ] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [ 2 ] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Background The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Task Force recently introduced a new clinical score termed quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) for identification of patients at risk of sepsis outside the intensive care unit (ICU). We attempted to compare the discriminatory capacity of the qSOFA versus the Systemic Inflammatory Response Syndrome (SIRS) score for predicting mortality, ICU-free days, and organ dysfunction-free days in patients with suspicion of infection outside the ICU. Methods The Weill Cornell Medicine Registry and Biobank of Critically Ill Patients is an ongoing cohort of critically ill patients, for whom biological samples and clinical information (including vital signs before and during ICU hospitalization) are prospectively collected. Using such information, qSOFA and SIRS scores outside the ICU (specifically, within 8 hours before ICU admission) were calculated. This study population was therefore comprised of patients in the emergency department or the hospital wards who had suspected infection, were subsequently admitted to the medical ICU and were included in the Registry and Biobank. Results One hundred fifty-two patients (67% from the emergency department) were included in this study. Sixty-seven percent had positive cultures and 19% died in the hospital. Discrimination of in-hospital mortality using qSOFA [area under the receiver operating characteristic curve (AUC), 0.74; 95% confidence intervals (CI), 0.66–0.81] was significantly greater compared with SIRS criteria (AUC, 0.59; 95% CI, 0.51–0.67; p  = 0.03). The qSOFA performed better than SIRS regarding discrimination for ICU-free days ( p  = 0.04), but not for ventilator-free days ( p  = 0.19), any organ dysfunction-free days ( p  = 0.13), or renal dysfunction-free days ( p  = 0.17). Conclusions In patients with suspected infection who eventually required admission to the ICU, qSOFA calculated before their ICU admission had greater accuracy than SIRS for predicting mortality and ICU-free days. However, it may be less clear whether qSOFA is also better than SIRS criteria for predicting ventilator free-days and organ dysfunction-free days. These findings may help clinicians gain further insight into the usefulness of qSOFA.

IntroductionSeveral methods have been developed to electronically monitor patients for severe sepsis, but few provide predictive capabilities to enable early intervention; furthermore, no severe sepsis prediction systems have been previously validated in a randomised study. We tested the use of a machine learning-based severe sepsis prediction system for reductions in average length of stay and in-hospital mortality rate.MethodsWe conducted a randomised controlled clinical trial at two medical-surgical intensive care units at the University of California, San Francisco Medical Center, evaluating the primary outcome of average length of stay, and secondary outcome of in-hospital mortality rate from December 2016 to February 2017. Adult patients (18+) admitted to participating units were eligible for this factorial, open-label study. Enrolled patients were assigned to a trial arm by a random allocation sequence. In the control group, only the current severe sepsis detector was used; in the experimental group, the machine learning algorithm (MLA) was also used. On receiving an alert, the care team evaluated the patient and initiated the severe sepsis bundle, if appropriate. Although participants were randomly assigned to a trial arm, group assignments were automatically revealed for any patients who received MLA alerts.ResultsOutcomes from 75 patients in the control and 67 patients in the experimental group were analysed. Average length of stay decreased from 13.0 days in the control to 10.3 days in the experimental group (p=0.042). In-hospital mortality decreased by 12.4 percentage points when using the MLA (p=0.018), a relative reduction of 58.0%. No adverse events were reported during this trial.ConclusionThe MLA was associated with improved patient outcomes. This is the first randomised controlled trial of a sepsis surveillance system to demonstrate statistically significant differences in length of stay and in-hospital mortality.Trial registrationNCT03015454.