Use of Unconventional Therapies in Super-refractory Status Epilepticus: A Case Report and Literature Review.

Super-refractory status epilepticus (SRSE) is a life-threatening condition characterized by the persistence or recurrence of seizures despite the use of first- and second-line antiepileptic drugs and the continuous infusion of anesthetics for more than 24 hours. This has always been a challenge for the physician, given the high mortality and morbidity related to this condition. Unfortunately, there are currently no definitive data to guide the therapy, since most of the therapeutic approaches regarding SRSE come from anecdotal evidence. Here, we present a case report of long-persisting new-onset SRSE treated with unconventional therapies recently reported to be successful such as ketamine, ketogenic diet, and tocilizumab, that could have played an important role in the management of this patient. A review of the literature regarding those is also included. SRSE has been reported to have long hospital length of stay, with a small percentage of patients returning to baseline functional status. Moreover, recent evidence showed that functional and cognitive outcome could depend on seizure duration, so prolonged duration of epileptic activity with abnormalities on the magnetic resonance imaging (MRI) could be seen as a reason to discontinue treatment. However, despite many weeks of seizures and a noncomforting MRI, our patient was discharged with a good functional status.

Prediction of ventilator-associated pneumonia outcomes according to the early microbiological response: a retrospective observational study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a leading infectious cause of morbidity in critically ill patients, yet current guidelines offer no indications for follow-up cultures. We aimed to evaluate the role of follow-up cultures and microbiological response 3 days after diagnosing VAP as predictors of short- and long-term outcomes. METHODS: We performed a retrospective analysis of a cohort prospectively collected from 2004 to 2017. VAP was diagnosed based on clinical, radiographical and microbiological criteria. For microbiological identification, a tracheobronchial aspirate was performed at diagnosis and repeated after 72 h. We defined three groups when comparing the two tracheobronchial aspirate results: persistence, superinfection and eradication of causative pathogens. RESULTS: 157 patients were enrolled in the study, among whom microbiological persistence, superinfection or eradication was present in 67 (48%), 25 (16%) and 65 (41%), respectively, after 72 h. Those with superinfection had the highest mortalities in the intensive care unit (p=0.015) and at 90 days (p=0.036), while also having the fewest ventilator-free days (p=0.019). Multivariable analysis revealed shock at VAP diagnosis (OR 3.43, 95% CI 1.25-9.40), Staphylococcus aureus isolation at VAP diagnosis (OR 2.87, 95% CI 1.06-7.75) and hypothermia at VAP diagnosis (OR 0.67, 95% CI 0.48-0.95, per +1°C) to be associated with superinfection. CONCLUSIONS: Our retrospective analysis suggests that VAP short- and long-term outcomes may be associated with superinfection in follow-up cultures. Follow-up cultures may help guide antibiotic therapy and its duration. Further prospective studies are necessary to verify our findings.

A rare pheochromocytoma complicated by cardiogenic shock and posterior reversible encephalopathy syndrome: case report.

BACKGROUND: Pheochromocytoma is a rare catecholamine-producing tumour that classically displays clinical manifestations related to alpha-adrenergic stimulation, including paroxysmal or sustained hypertension. However, it may occasionally be complicated by life-threatening crisis, leading to refractory acute heart dysfunction in the most severe cases. CASE SUMMARY: A 28-year-old woman was admitted to intensive care unit due to hypertensive crisis causing pulmonary oedema, Takotsubo cardiomyopathy, and metabolic acidosis. Due to cardiogenic shock, she required venoarterial extracorporeal membrane oxygenation and IMPELLA implantation. A computed tomography scan revealed a 5 cm tumour of the left adrenal gland compatible with pheochromocytoma The clinical course was complicated by acute kidney injury requiring renal replacement therapy and posterior reversible encephalopathy syndrome (PRES). Pharmacological treatment with alpha lityc agents (including urapidil, dexmedetomidine, and doxazosin at maximum daily dose) and beta blockers, together with left videolaparoscopic adrenalectomy, led to progressive blood pressure control and resolution of the neurological symptoms. DISCUSSION: Pheochromocytoma crisis turned into a potential catastrophic scenario, characterized by refractory cardiogenic shock requiring circulatory supportive devices and PRES. Alpha-antagonists and beta-blockers were the gold standard pharmacological treatment. A multidisciplinary decision-algorithm was necessary to successfully manage this complex clinical setting.

Predictive Performance of Risk Factors for Multidrug-Resistant Pathogens in Nosocomial Pneumonia.

Rationale: In 2017, the International European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Microbiology and Infectious Diseases/Latin American Thoracic Society (European) guidelines defined new risk factors for multidrug-resistant (MDR) pathogens in patients with nosocomial pneumonia.Objectives: To assess the predictive performance of these newly defined risk factors for MDR pathogens.Methods: We enrolled 507 adult patients with nosocomial pneumonia who were treated in six intensive care units at the Hospital Clinic of Barcelona in Spain. Of the 503 patients at high MDR pathogen and mortality risk, 275 (54%) had no septic shock and 228 (46%) had septic shock.Results: Admission to hospital settings with high rates of MDR pathogens (n = 421; 83%) and prior antibiotic use (n = 399; 79%) showed the highest prevalence in the overall population, with sensitivities of 92% and 85% and negative predictive values of 85% and 82%, respectively. However, low specificities and low positive predictive values were found. Previous respiratory MDR pathogen isolation was less common (n = 17; 3%) but presented a specificity and positive predictive value of 100%. The area under the receiver operating characteristic curve was less than 0.6 for all risk factors and combinations.Conclusions: The risk factors proposed by the European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Microbiology and Infectious Diseases/Latin American Thoracic Society showed low accuracy for predicting MDR pathogens in intensive care unit acquired pneumonia (ICU-AP). Admission to hospital settings with high rates of MDR pathogens and prior antibiotic use were the most prevalent risk factors, with a high sensitivity for predicting these microorganisms; prior positive cultures for MDR pathogens showed high specificity but very low sensitivity. Combinations of risk factors did not show any great accuracy for predicting these microorganisms. Further studies assessing combined strategies of risk stratification and complementary methods are now warranted.

Methicillin-susceptible staphylococcus aureus in community-acquired pneumonia: Risk factors and outcomes.

OBJECTIVES: We aimed to describe the prevalence, risk factors and outcomes of Methicillin-susceptible S. aureus (MSSA) community-acquired pneumonia (CAP) and compare them with those associated with CAP due to Streptococcus pneumoniae, the most frequent causative microorganism, in a large cohort of patients. METHODS: This was an observational study of prospectively collected data of consecutive adults with CAP and a definitive etiology enrolled between 2004 and 2018. Patients were divided into MSSA CAP and pneumococcal CAP groups for analysis. RESULTS: A microbial etiology was established in 1,548 (33%) cases: S. aureus caused 6% of microbiologically-confirmed CAP cases. In the latter, 52 were due to MSSA (60% of S. aureus CAP cases, and 3% of microbiologically-confirmed CAP cases) and 34 were due to MRSA (40% of S. aureus CAP cases, and 2% of microbiologically-confirmed CAP cases). S. pneumoniae was identified in 734 (47%) microbiologically-confirmed CAP cases. The presence of fever was independently associated with a lower risk of MSSA CAP (OR 0.53; 95% CI, 0.28-0.99). Patients with MSSA CAP had higher 30-day mortality than patients with pneumococcal CAP, both before and after adjustment for potential confounders (21% vs 7%, p = 0.002). MSSA was independently associated with 30-day mortality in the overall population. CONCLUSION: MSSA CAP was associated with worse outcomes than pneumococcal CAP in our cohort. MSSA was an independent factor of mortality.

Is ventilated hospital-acquired pneumonia a worse entity than ventilator-associated pneumonia?

INTRODUCTION: Nosocomial pneumonia develops after ≥48 h of hospitalisation and is classified as ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP); the latter may require mechanical ventilation (V-HAP) or not (NV-HAP). MAIN FINDINGS: VAP and HAP affect a significant proportion of hospitalised patients and are characterised by poor clinical outcomes. Among them, V-HAP has the greatest 28-day mortality rate followed by VAP and NV-HAP (27.8% versus 18% versus 14.5%, respectively). However, no differences in terms of pathophysiology, underlying microbiological pathways and subsequent therapy have been identified. International guidelines suggest specific flow charts to help clinicians in the therapeutic management of such diseases; however, there are no specific recommendations beyond VAP and HAP classification. HAP subtypes are scarcely considered as different entities and the lack of data from the clinical scenario limits any final conclusion. Hopefully, recent understanding of the pathophysiology of such diseases, as well as the discovery of new therapies, will improve the outcome associated with such pulmonary infections. CONCLUSION: Nosocomial pneumonia is a multifaced disease with features of pivotal interest in critical care medicine. Due to the worrisome data on mortality of patients with nosocomial pneumonia, further prospective studies focused on this topic are urgently needed.

Promoting the use of social networks in pneumonia.

BACKGROUND: Pneumonia is a serious health concern, but it does not attract the attention it warrants. Perhaps this is due to a lack of understanding of the real extent of this infectious disease in the general population. METHODS: A literature review was performed to assess the role of social networks as a means to raise awareness over pneumonia worldwide and increase its visibility. RESULTS: In 2017, approximately 800,000 children under 5 years and approximately one million older people died of pneumonia. The importance of this pathology remains underestimated, despite the publication of many articles, comments, and editorials dedicated to rectifying the imbalance and to reduce its impact and associated mortality. Current misperceptions about pneumonia are alarming. Education and awareness are essential in the fight against this major public health threat; in this endeavor, social networks can be used to distribute science-based information about the disease and thus raise awareness among the general public about the dangers it poses. Approximately 3.8 billion people were using social media at the beginning of 2020, representing more than half of the world's population. CONCLUSION: Social networks offer a valuable tool for disseminating scientific information about pneumonia, increasing its visibility, and in general raising awareness about this preventable disease.

Gender differences in community-acquired pneumonia.

INTRODUCTION: Community-acquired pneumonia (CAP) is the most common type of lower respiratory tract infection and a major cause of morbidity and mortality in adults worldwide. Sex and gender play an active role in the incidence and outcomes of major infectious diseases, including CAP. EVIDENCE ACQUISITION: We searched the following electronic databases from January 2001 to December 2018: MEDLINE, EMBASE, CINHAIL, CENTRAL (Cochrane Central register of Controlled Trials), DARE (Database of Abstracts of Reviews of Effectiveness), Cochrane Database of Systematic Reviews and ACP Journal Club database. EVIDENCE SYNTHESIS: Several studies have reported higher male susceptibility to pulmonary infections and higher risk of death due to sepsis. Biological differences (e.g. hormonal cycles and cellular immune-mediated responses) together with cultural, behavioral and socio-economic differences are important determinants of the course and outcome of CAP. However, gender-related bias in the provision of care and use of hospital resources has been reported among women, resulting in delayed hospital admission and consequently necessary care. CONCLUSIONS: CAP is more severe in males than in females, leading to higher mortality in males, especially in older age. To identify gender differences in CAP can guide patient's prognostication and management.

Community-acquired pneumonia in critically ill very old patients: a growing problem.

Very old (aged ≥80 years) adults constitute an increasing proportion of the global population. Currently, this subgroup of patients represents an important percentage of patients admitted to the intensive care unit. Community-acquired pneumonia (CAP) frequently affects very old adults. However, there are no specific recommendations for the management of critically ill very old CAP patients. Multiple morbidities, polypharmacy, immunosenescence and frailty contribute to an increased risk of pneumonia in this population. CAP in critically ill very old patients is associated with higher short- and long-term mortality; however, because of its uncommon presentation, diagnosis can be very difficult. Management of critically ill very old CAP patients should be guided by their baseline characteristics, clinical presentation and risk factors for multidrug-resistant pathogens. Hospitalisation in intermediate care may be a good option for critical ill very old CAP patients who do not require invasive procedures and for whom intensive care is questionable in terms of benefit.

Ventilator-associated pneumonia: new principles guiding empiric antibiotic therapy.

PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is a serious event in critically ill patients. We aim to review the most recent evidences about VAP, including its cause, the main differences between the American and European guidelines in the definition of risk factors for multidrug-resistant pathogens, the main principles guiding empirical antibiotic treatment, and the potential role of molecular diagnostic tests. RECENT FINDINGS: The 2016 ATS/IDSA and the 2017 ERS/ESICM/ESCMID/ALAT guidelines provide different approaches for the management of VAP. Both guidelines highlight the need to use local epidemiological data for antibiotic choice; however, they identify different risk factors that can assist with decision making when local data are not available. Nevertheless, validation studies of the American guidelines suggest that empiric antibiotic therapy based on risk factors may lead to an overuse of broad-spectrum antibiotics. Rapid diagnostic tests may allow a faster identification of VAP cause, resulting in more adequate antimicrobial therapy and reduced exposition to broad-spectrum antibiotics. SUMMARY: Clinical studies should be conducted to evaluate the benefits of implementing guidelines and new approaches such as combinations of clinical data with rapid diagnostic tests; meantime adaptations of guidelines to local settings should be carried out by a local multidisciplinary expert team.

An overview of guidelines for the management of hospital-acquired and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria.

PURPOSE OF REVIEW: Multidrug-resistant (MDR) Gram-negative pathogens in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are associated with poor clinical outcomes. These pathogens represent a global threat with few therapeutic options. In this review, we discuss current guidelines for the empiric management of HAP/VAP caused by MDR Gram-negative pathogens. RECENT FINDINGS: The incidence of MDR Gram-negative bacteria is rising among cases of nosocomial pneumonia, such that it is now becoming a significant challenge for clinicians. Adherence to international guidelines may ensure early and adequate antimicrobial therapy, guided by local microbiological data and awareness of the risk factors for MDR bacteria. SUMMARY: Due to the increasing prevalence of HAP/VAP caused by MDR Gram-negative pathogens, management should be guided by the local ecology and the patient's risk factors for MDR pathogens. The main risk factors are prior hospitalization for at least 5 days, prior use of broad-spectrum antibiotics, prior colonization with resistant pathogens, admission to hospital settings with high rates of MDR pathogens, and septic shock at the time of diagnosis with nosocomial pneumonia.

Pneumocystis pneumonia in the twenty-first century: HIV-infected versus HIV-uninfected patients.

Introduction: Pneumocystis pneumonia (PcP) has classically been described as a serious complication in patients infected with the human immunodeficiency virus (HIV). However, the emerging number of conditions associated with immunosuppression has led to its appearance in other patient populations. Areas covered: This article reviews the most recent publications on PcP in the HIV-infected and HIV-uninfected population, focusing on epidemiology, diagnostic, therapy and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles including randomized clinical trials, meta-analyses, observational studies and clinical reviews. Expert opinion: The growing incidence of Pneumocystis infection in the HIV-uninfected population suggests the need for new global epidemiological studies in order to identify the true scale of the disease in this population. These data would allow us to improve diagnosis, therapeutic strategies, and clinical management. It is very important that both patients and physicians realize that HIV-uninfected patients are at risk of PcP and that rapid diagnosis and early initiation of treatment are associated with better prognosis. Currently, in-hospital mortality rates are very high: 15% for HIV-infected patients and 50% in some HIV-uninfected patients. Therefore, adequate preventive measures should be implemented to avoid the high mortality rates seen in recent decades.

Ceftobiprole for the treatment of pneumonia

Ceftobiprole is a fifth-generation cephalosporin with potent antimicrobial activity against Gram positive and Gram-negative bacteria. It has been approved in major European countries for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia (VAP). Ceftobiprole is currently in a phase 3 clinical program for registration in the U. S. In 2015, it was designated as an infectious disease product qualified for the treatment of lung and skin infections by the FDA. The efficacy of ceftobiprole in pneumonia has been demonstrated in two-phase III clinical trials conducted in patients with CAP and HAP. The recommended dose in the adult with pneumonia is 500 mg every 8 h infused in 2 h; in case of renal failure, the regimen of administration must be adjusted according to the patient's renal function. It is not necessary to adjust the dose according to gender, age, body weight or liver failure. In case of hyperfiltration, an extension to 4 h infusion of the 500mg TID is required

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Impact of Cefotaxime Non-susceptibility on the Clinical Outcomes of Bacteremic Pneumococcal Pneumonia.

BACKGROUND: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. METHODS: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses. RESULTS: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate. CONCLUSION: Despite the prevalence of cefotaxime, non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.

Ventilator-Associated Pneumonia and PaO2/FIO2 Diagnostic Accuracy: Changing the Paradigm?

BACKGROUND: Ventilator-associated pneumonia (VAP) is associated to longer stay and poor outcomes. Lacking definitive diagnostic criteria, worsening gas exchange assessed by PaO2/FIO2 ≤ 240 in mmHg has been proposed as one of the diagnostic criteria for VAP. We aim to assess the adequacy of PaO2/FIO2 ≤ 240 to diagnose VAP. METHODS: Prospective observational study in 255 consecutive patients with suspected VAP, clustered according to PaO2/FIO2 ≤ 240 vs. > 240 at pneumonia onset. The primary analysis was the association between PaO2/FIO2 ≤ 240 and quantitative microbiologic confirmation of pneumonia, the most reliable diagnostic gold-standard. RESULTS: Mean PaO2/FIO2 at VAP onset was 195 ± 82; 171 (67%) cases had PaO2/FIO2 ≤ 240. Patients with PaO2/FIO2 ≤ 240 had a lower APACHE-II score at ICU admission; however, at pneumonia onset they had higher CPIS, SOFA score, acute respiratory distress syndrome criteria and incidence of shock, and less microbiological confirmation of pneumonia (117, 69% vs. 71, 85%, p = 0.008), compared to patients with PaO2/FIO2 > 240. In multivariate logistic regression, PaO2/FIO2 ≤ 240 was independently associated with less microbiological confirmation (adjusted odds-ratio 0.37, 95% confidence interval 0.15-0.89, p = 0.027). The association between PaO2/FIO2 and microbiological confirmation of VAP was poor, with an area under the ROC curve 0.645. Initial non-response to treatment and length of stay were similar between both groups, while hospital mortality was higher in patients with PaO2/FIO2 ≤ 240. CONCLUSION: Adding PaO2/FIO2 ratio ≤ 240 to the clinical and radiographic criteria does not help in the diagnosis of VAP. PaO2/FIO2 ratio > 240 does not exclude this infection. Using this threshold may underestimate the incidence of VAP.

Risk and Prognostic Factors in Very Old Patients with Sepsis Secondary to Community-Acquired Pneumonia.

BACKGROUND: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4219 patients hospitalized with CAP during the study period, 1238 (29%) were very old. The prevalence of sepsis in this age group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis.

Pure Viral Sepsis Secondary to Community-Acquired Pneumonia in Adults: Risk and Prognostic Factors.

We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Pure viral sepsis was found in 3% of all patients (138 of 4028) admitted to the emergency department with a diagnosis of CAP, 19% of those with CAP (138 of 722) admitted to the intensive care unit, and 61% of those (138 of 225) with a diagnosis of viral CAP. Our data indicate that males and patients aged ≥65 years are at increased risk of viral sepsis.

Multidrug Resistant Gram-Negative Bacteria in Community-Acquired Pneumonia.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .