Outpatient management of community-acquired pneumonia.

PURPOSE OF REVIEW: Although most patients with community-acquired pneumonia (CAP) are treated as outpatients, the majority of data regarding CAP management is provided by hospitals, either from emergency department or inpatients. This was already noted in the first CAP guidelines, published in 1993, and the challenges regarding the outpatient management of CAP persist nowadays. These include the uncertainty of the initial diagnosis and risk stratification, the empirical choice of antibiotics, the overgrowing of antibiotic resistance bacteria and the relative scarcity of novel antibiotics. RECENT FINDINGS: New molecular biology methods have changed the etiologic perspective of CAP, unveiling the role of virus. Diagnostic uncertainty may lead to antibiotic overuse and bacteria resistance. Novel antibiotics along with diagnostic improvement, related to the use of lung ultrasound and point-of-care biomarkers testing, may help to improve CAP treatment. Prevention, especially the use of antipneumococcal vaccine, is instrumental in reducing the burden of disease. SUMMARY: Most of CAP cases are managed in the outpatient setting. However, most research is focused on hospitalized severe patients. New and awaited advances might contribute to aid diagnosis, cause and assessment of patients with CAP in the community. This knowledge might prove decisive in improving outcomes, as well as to the execution of stewardship programs that maintain current antibiotics, safeguard future ones and reinforce prevention.

Outpatient management of community-acquired pneumonia.

PURPOSE OF REVIEW: The first guidelines on community-acquired pneumonia (CAP) were published in 1993, but since then many of the challenges regarding the outpatient management of CAP persist. These include the difficulty in establishing the initial clinical diagnosis, its risk stratification, which will dictate the place of treatment, the empirical choice of antibiotics, the relative scarcity of novel antibiotics and the importance of knowing local microbiological susceptibility patterns. RECENT FINDINGS: New molecular biology methods have changed the etiologic perspective of CAP, especially the contribution of virus. Lung ultrasound and biomarkers might aid diagnosis and severity stratification in the outpatient setting. Antibiotic resistance is a growing problem that reinforces the importance of novel antibiotics. And finally, prevention and the use of anti-pneumococcal vaccine are instrumental in reducing the burden of disease. SUMMARY: Most of CAP cases are managed in the community; however, most research comes from hospitalized severe patients. New and awaited advances might contribute to aid diagnosis, cause and assessment of patients with CAP in the community. This knowledge might prove decisive in the execution of stewardship programmes that maintain current antibiotics, safeguard future ones and reinforce prevention.

Molecular antimicrobial susceptibility testing in sepsis.

Rapidly detecting and identifying pathogens is crucial for appropriate antimicrobial therapy in patients with sepsis. Conventional diagnostic methods have been a great asset to medicine, though they are time consuming and labor intensive. This work will enable healthcare professionals to understand the bacterial community better and enhance their diagnostic capacity by using novel molecular methods that make obtaining quicker, more precise results possible. The authors discuss and critically assess the merits and drawbacks of molecular testing and the added value of these tests, including the shift turnaround time, the implication for clinicians' decisions, gaps in knowledge, future research directions and novel insights or innovations. The field of antimicrobial molecular testing has seen several novel insights and innovations to improve the diagnosis and management of infectious diseases.

Sepsis is a life-threatening reaction to an infection. This infection is normally caused by a bacteria. Identifying the bacteria that has caused the infection is very important to choosing the best treatment. This is usually done using molecular testing. This article discusses the advantages and disadvantages of molecular testing, which tests are available and the value of these tests in clinical practice, the implication of molecular tests for clinicians' decisions and the gaps in our knowledge. It also discusses future innovations in molecular testing.

Epidemiology and Burden of Ventilator-Associated Pneumonia among Adult Intensive Care Unit Patients: A Portuguese, Multicenter, Retrospective Study (eVAP-PT Study).

Ventilator-associated pneumonia (VAP) is a prevailing nosocomial infection in critically ill patients requiring invasive mechanical ventilation (iMV). The impact of VAP is profound, adversely affecting patient outcomes and placing a significant burden on healthcare resources. This study assessed for the first time the contemporary VAP epidemiology in Portugal and its burden on the healthcare system and clinical outcomes. Additionally, resource consumption (duration of iMV, intensive care unit (ICU), hospital length of stay (LOS)) and empirical antimicrobial therapy were also evaluated. This multicenter, retrospective study included patients admitted to the hospital between July 2016 and December 2017 in a participating ICU, who underwent iMV for at least 48 h. Patients with a VAP diagnosis were segregated for further analysis (n = 197). Control patients, ventilated for >48 h but without a VAP diagnosis, were also included in a 1:1 ratio. Cumulative VAP incidence was computed. All-cause mortality was assessed at 28, 90, and 365 days after ICU admission. Cumulative VAP incidence was 9.2% (95% CI 8.0-10.5). The all-cause mortality rate in VAP patients was 24.9%, 34.0%, and 40.6%, respectively, and these values were similar to those observed in patients without VAP diagnosis. Further, patients with VAP had significantly longer ICU (27.5 vs. 11.0 days, p < 0.001) and hospital LOS (61 vs. 35.9 days, p < 0.001), more time under iMV (20.7 vs. 8.0 days, p < 0.001) and were more often subjected to tracheostomy (36.5 vs. 14.2%; p < 0.001). Patients with VAP who received inappropriate empirical antimicrobials had higher 28-day mortality, 34.3% vs. 19.5% (odds ratio 2.16, 95% CI 1.10-4.23), although the same was not independently associated with 1-year all-cause mortality (p = 0.107). This study described the VAP impact and burden on the Portuguese healthcare system, with approximately 9% of patients undergoing iMV for >48 h developing VAP, leading to increased resource consumption (longer ICU and hospital LOS). An unexpectedly high incidence of inappropriate, empirical antimicrobial therapy was also noted, being positively associated with a higher mortality risk of these patients. Knowledge of the Portuguese epidemiology characterization of VAP and its multidimensional impact is essential for efficient treatment and optimized long-term health outcomes of these patients.

New technologies in airway management: A review.

The evolution of medical knowledge and technological growth have contributed to the development of different techniques and devices for airway management. These appear to play a role in optimizing the number of attempts and overall success, ultimately reducing the negative consequences of airway manipulation. In this literature review, we highlight the recent evidence regarding new technologies applied to airway management. Before intubation, every patient should have an individualized structured airway management plan. Technology can help with both airway evaluation and tracheal intubation. Point-of-care cervical ultrasound and artificial intelligence models with automated facial analysis have been used to predict difficult airways. Various devices can be used in airway management. This includes a robotic video endoscope that guides intubation based on real image recognition, a laryngeal mask with a non-inflatable cuff that tries to reduce local complications, video laryngeal masks that are able to confirm the correct position and facilitate intubation, Viescope™, a videolaryngoscope developed for combat medicine with a unique circular blade, a system that uses cervical transillumination for glottis identification in difficult airways and Vivasight SL™ tracheal tube, which has a high-resolution camera at its tip guaranteeing visual assurance of tube position as well as guiding bronchial blocker position. To conclude, we detailed the challenges in airway management outside the operating room as well as described suction-assisted laryngoscopy and airway decontamination technique for contaminated airways. Further research in the clinical setting is recommended to better support the use of these technologies.

ß-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity.

Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time ß-lactam antibiotic dose adjustments according to the patient's condition are critical. The continuous infusion of ß-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to ß-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that ß-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time ß-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.

Optimizing Antimicrobial Drug Dosing in Critically Ill Patients.

A fundamental step in the successful management of sepsis and septic shock is early empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens; (2) they should be administered in the appropriate dose, (3) by the correct route, and (4) using the correct mode of administration to achieve successful concentration at the infection site. In critically ill patients, antimicrobial dosing is a common challenge and a frequent source of errors, since these patients present deranged pharmacokinetics, namely increased volume of distribution and altered drug clearance, which either increased or decreased. Moreover, the clinical condition of these patients changes markedly over time, either improving or deteriorating. The consequent impact on drug pharmacokinetics further complicates the selection of correct drug schedules and dosing during the course of therapy. In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. We aim to review the available literature to assess the challenges, impact, and tools to optimize individualization of antimicrobial dosing to maximize exposure and effectiveness in critically ill patients.

Pneumocephalus Following an Accidental Dural Puncture, Treated Using Hyperbaric Oxygen Therapy. A Case Report.

INTRODUCTION: Neuraxial techniques, including epidural anaesthesia, are often used for perioperative pain control and are generally safe. However, both transient, mild and even severe, life-threatening neurologic complications can occur. CASE PRESENTATION: A seventy-eight-year-old man was admitted to the hospital for a radical nephrectomy plus transurethral resection due to kidney and bladder cancer. During the epidural exploration, an accidental dural puncture was noted. This was followed by the patient complaining of an intense headache. The epidural catheter was placed in a different location, and surgery was performed uneventfully. The patient presented with confusion, agitation, vertical nystagmus, vision loss, and paraparesis about two hours later. The epidural levobupivacaine and morphine infusion were stopped, followed by motor block resolution. A computerized head-tomography scan showed extra-axial multiple air spots involving the frontal and temporal lobes. Emergent hyperbaric oxygen therapy was commenced. After a single session, there was complete resolution of all symptoms and a marked reduction in the number and volume of the extra-axial air visible on the CT scan. CONCLUSIONS: Although rare, pneumocephalus is a well-recognized complication of a dural puncture. Its rapid recognition in a patient with new-onset neurological symptoms and early treatment with hyperbaric oxygen therapy allows rapid clinical and imaging resolution and an improved prognosis.

suPAR in the assessment of post intensive care unit prognosis: a pilot study. / suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto.

OBJECTIVE: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. METHODS: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. RESULTS: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). CONCLUSION: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.

OBJETIVO: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. MÉTODOS: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. RESULTADOS: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). CONCLUSÃO: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

Critically ill patients with high predicted mortality: Incidence and outcome / Pacientes en cuidados intensivos con alta mortalidad prevista: Incidencia y evolución

Objective As calculated by the severity scores, an unknown number of patients are admitted to the Intensive Care Unit (ICU) with a very high risk of death. Clinical studies have poorly addressed this population, and their prognosis is largely unknown. Design Post hoc analysis of a multicenter, cohort, longitudinal, observational, retrospective study (CIMbA). Setting Sixteen Portuguese multipurpose ICUs. Patients Patients with a Simplified Acute Physiology Score II (SAPS II) predicted hospital mortality above 80% on admission to the ICU (high-risk group); A comparison with the remaining patients was obtained. Interventions None. Main Variables of Interest Hospital, 30 days, 1 year mortality. Results We identified 4546 patients (59.9% male), 12.2% of the whole population. Their SAPS II predicted hospital mortality was 89.0±5.8%, whilst the observed mortality was lower, 61.0%. This group had higher mortality, both during the first 30 days (aHR 3.52 [95% CI 3.34–3.71]) and from day 31 to day 365 after ICU admission (aHR 1.14 [95%CI 1.04–1.26]), respectively. However, their hospital standardized mortality ratio was similar to the other patients (0.69 vs. 0.69, P=.92). At one year of follow-up, 30% of patients in the high-risk group were alive. Conclusions Roughly 12% of patients admitted to the ICU for more than 24h had a SAPS II score predicted mortality above 80%. Their hospital standardized mortality was similar to the less severe population and 30% were alive after one year of follow-up. (AU)

Objetivo Según las escalas de gravedad, un número indeterminado de pacientes ingresan en la Unidad de Cuidados Intensivos (UCI) con riesgo de muerte muy elevado. Este grupo ha sido poco abordado en los estudios clínicos y se desconoce en gran medida su pronóstico. Diseño Análisis post-hoc de estudio multicéntrico, de cohortes, longitudinal, observacional y retrospectivo (CIMbA). Âmbito Dieciséis UCI polivalentes portuguesas. Pacientes Pacientes con mortalidad hospitalaria prevista en el Simplified Acute Physiology Score II (SAPS II) superior al 80% nel ingreso en la UCI (grupo de alto riesgo); se compararon con los restantes. Intervenciones Ninguna. Variables de interés principals Mortalidad hospitalaria, a 30 días y 1 año. Resultados Se identificaron 4546 pacientes (59.9% hombres), 12.2% da población. La mortalidad hospitalaria estimada por lo SAPS II fue de 89.0±5.8%, aunque la observada fue inferior, 61.0%. Este grupo presentó mayor mortalidad, tanto durante los primeros 30 días (aHR 3.52 [IC 95%: 3.34–3.71]) y desde el día 31 hasta el día 365 después del ingreso en UCI (aHR 1.14 [IC 95%: 1.04–1.26]). Sin embargo, su índice de mortalidad hospitalaria estandarizada fue similar a los otros pacientes (0.69 vs. 0.69; P=.92). Al primer año de seguimiento, 30% de los pacientes de alto riesgo estaban vivos. ConclusionesAproximadamente 12% de los pacientes ingresados en la UCI durante más de 24 horas tenían una mortalidad prevista por SAPS II superior al 80%. Su mortalidad hospitalaria estandarizada fue similar a la de la población menos grave y el 30% estaban vivos después de un año de seguimiento. (AU)

suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto / suPAR in the assessment of post intensive care unit prognosis: a pilot study

RESUMO Objetivo: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. Métodos: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. Resultados: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). Conclusão: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

ABSTRACT Objective: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. Methods: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. Results: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). Conclusion: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.