Bloodstream infections as a marker of community-acquired sepsis severity. Results from the Portuguese community-acquired sepsis study (SACiUCI study)

Funding Information: This work was mostly supported by an unrestricted grant from ASSUCIP (Associação dos Amigos da Unidade de Cuidados Intensivos Polivalente, Hospital Geral de Santo António, Porto, Portugal) as well as by grants from GIS (Grupo de Infecção e Sepsis, Hospital de São João, Porto, Portugal) Merck Sharp & Dohme and Eli Lilly. CL received a grant from Fundação para a Ciência e Tecnologia (PIC/IC/83312/2007). All other authors report that they have no other competing interests to declare related to the topic of this manuscript.Clin Microbiol Infect 2013; 19: 242-248 The impact of bloodstream infection (BSI) on admission to hospital on the outcome of patients with community-acquired sepsis (CAS) admitted to intensive-care units (ICU) is largely unknown. We selected 803 adult patients consecutively admitted with CAS to one of 17 Portuguese ICU, in whom blood cultures were collected before initiation of antibiotic therapy during a 12-month period. A BSI was identified on hospital admission in 160 (19.9%) patients. Those with and without BSI had similar mean Simplified Acute Physiology Score (SAPS) II and age. The presence of BSI was independently associated with mortality in ICU (adjusted odds ratio 1.86; 95% confidence interval 1.20-2.89; p 0.005). On the 4th day in ICU, patients with BSI were found to be significantly more dependent on vasopressor support (p 0.002) but not on ventilatory support. Cumulative ICU mortality was significantly higher in BSI patients from the 9th day onwards. A seasonal variation of BSI isolates was noted: gram-negative BSI were more common in the summer, whereas in the winter, gram-positive infections were more frequent (p 0.024), without mortality differences.publishersversionpublishe

Bloodstream infections as a marker of community-acquired sepsis severity. Results from the Portuguese community-acquired sepsis study (SACiUCI study)

Funding Information: This work was mostly supported by an unrestricted grant from ASSUCIP (Associação dos Amigos da Unidade de Cuidados Intensivos Polivalente, Hospital Geral de Santo António, Porto, Portugal) as well as by grants from GIS (Grupo de Infecção e Sepsis, Hospital de São João, Porto, Portugal) Merck Sharp & Dohme and Eli Lilly. CL received a grant from Fundação para a Ciência e Tecnologia (PIC/IC/83312/2007). All other authors report that they have no other competing interests to declare related to the topic of this manuscript.Clin Microbiol Infect 2013; 19: 242-248 The impact of bloodstream infection (BSI) on admission to hospital on the outcome of patients with community-acquired sepsis (CAS) admitted to intensive-care units (ICU) is largely unknown. We selected 803 adult patients consecutively admitted with CAS to one of 17 Portuguese ICU, in whom blood cultures were collected before initiation of antibiotic therapy during a 12-month period. A BSI was identified on hospital admission in 160 (19.9%) patients. Those with and without BSI had similar mean Simplified Acute Physiology Score (SAPS) II and age. The presence of BSI was independently associated with mortality in ICU (adjusted odds ratio 1.86; 95% confidence interval 1.20-2.89; p 0.005). On the 4th day in ICU, patients with BSI were found to be significantly more dependent on vasopressor support (p 0.002) but not on ventilatory support. Cumulative ICU mortality was significantly higher in BSI patients from the 9th day onwards. A seasonal variation of BSI isolates was noted: gram-negative BSI were more common in the summer, whereas in the winter, gram-positive infections were more frequent (p 0.024), without mortality differences.publishersversionpublishe

Should C-reactive protein concentration at ICU discharge be used as a prognostic marker?

<p>Abstract</p> <p>Background</p> <p>About one third of hospital mortality in critically ill patients occurs after Intensive Care Unit (ICU) discharge. Some authors have recently hypothesized that unresolved or latent inflammation and sepsis may be an important factor that contributes to death following successful discharge from the ICU.</p> <p>Aim</p> <p>The aim of our study was to determine the ability of the clinical and inflammatory markers at ICU discharge to predict post-ICU mortality.</p> <p>Methods</p> <p>A prospective observational cohort study was conducted during a 14-month period in an 8 bed polyvalent ICU. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, Therapeutic Intervention Scoring System-28 (TISS-28), C-reactive protein (CRP), white cell count (WCC) and body temperature of the day of ICU discharge were collected from patients who survived their first ICU admission.</p> <p>Results</p> <p>During this period 156 patients were discharged alive from the ICU. A total of 29 patients (18.6%) died after ICU discharge. There were no differences in clinical and demographic characteristics between survivors and nonsurvivors. C-reactive protein levels at ICU discharge were not significantly different between survivors and nonsurvivors. The area under receiver operating characteristics curves of APACHE II, SAPS II, SOFA, TISS-28, CRP, WCC and body temperature at ICU discharge as prognostic markers of hospital death were 0.76 (95% confidence interval (CI) 0.67-0.86); 0.75 (95% CI 0.66-0.85); 0.72 (95% CI 0.62-0.83); 0.64 (95% CI 0.52-0.77); 0.55 (95% CI 0.43-0.67); 0.55 (95% CI 0.42-0.66) and 0.54 (95% CI 0.44-0.67) respectively. The hospital mortality rate of the patients with CRP <5, 5-10, >10 mg/dL was 15.1%, 16.1% and 33.3% respectively (p = NS).</p> <p>Conclusions</p> <p>At ICU discharge serum CRP concentration was a poor marker of post-ICU prognosis. Post-ICU death appears to be unrelated to the persistent inflammatory response.</p

Genética de populações naturais.

Em um cenário de fragmentação de habitats, populações anteriormente contínuas são subdivididas em conjuntos de populações locais menores que podem estar isoladas em maior ou menor grau, dependendo da distribuição espacial dos fragmentos e do poder de dispersão inerente às espécies. Técnicas moleculares, além de permitirem a identificação dos efeitos da fragmentação sobre o complemento genético das populações remanescentes, também têm sido úteis em programas de manejo para conservação genética de populações

Core Outcome Measures for Trials in People with Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery

OBJECTIVES: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019. DESIGN: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery. SETTING: International. PATIENTS: About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respiratory failure, assessed by the need for respiratory support based on the World Health Organization Clinical Progression Scale, was considered pragmatic, objective, and with broad applicability to various clinical scenarios. The Sequential Organ Failure Assessment was recommended for multiple organ failure, because it was routinely used in trials and clinical care, well validated, and feasible. The Modified Medical Research Council measure for shortness of breath, with minor adaptations (recall period of 24 hr to capture daily fluctuations and inclusion of activities to ensure relevance and to capture the extreme severity of shortness of breath in people with coronavirus disease 2019), was regarded as fit for purpose for this indication. The recovery measure was developed de novo and defined as the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness, using a 5-point Likert scale, and was endorsed. CONCLUSIONS: The coronavirus disease 2019 core outcome set recommended core outcome measures have content validity and are considered the most feasible and acceptable among existing measures. Implementation of the core outcome measures in trials in coronavirus disease 2019 will ensure consistency and relevance of the evidence to inform decision-making and care of patients with coronavirus disease 2019

What influences national and foreign physicians’ geographic distribution? An analysis of medical doctors’ residence location in Portugal

Background The debate over physicians’ geographical distribution has attracted the attention of the economic and public health literature over the last forty years. Nonetheless, it is still to date unclear what influences physicians’ location, and whether foreign physicians contribute to fill the geographical gaps left by national doctors in any given country. The present research sets out to investigate the current distribution of national and international physicians in Portugal, with the objective to understand its determinants and provide an evidence base for policymakers to identify policies to influence it. Methods A cross-sectional study of physicians currently registered in Portugal was conducted to describe the population and explore the association of physician residence patterns with relevant personal and municipality characteristics. Data from the Portuguese Medical Council on physicians’ residence and characteristics were analysed, as well as data from the National Institute of Statistics on municipalities’ population, living standards and health care network. Descriptive statistics, chi-square tests, negative binomial and logistic regression modelling were applied to determine: (a) municipality characteristics predicting Portuguese and International physicians’ geographical distribution, and; (b) doctors’ characteristics that could increase the odds of residing outside the country’s metropolitan areas. Results There were 39,473 physicians in Portugal in 2008, 51.1% of whom male, and 40.2% between 41 and 55 years of age. They were predominantly Portuguese (90.5%), with Spanish, Brazilian and African nationalities also represented. Population, Population’s Purchasing Power, Nurses per capita and Municipality Development Index (MDI) were the municipality characteristics displaying the strongest association with national physicians’ location. For foreign physicians, the MDI was not statistically significant, while municipalities’ foreign population applying for residence appeared to be an additional positive factor in their location decisions. In general, being foreigner and male resulted to be the physician characteristics increasing the odds of residing outside the metropolitan areas. However, among the internationals, older doctors were more likely to reside outside metropolitan areas. Being Spanish or Brazilian (but not of African origin) was found to increase the odds of being based outside the Lisbon and Oporto metropolitan areas. Conclusions The present study showed the relevance of studying one country’s physician population to understand the factors driving national and international doctors’ location decisions. A more nuanced understanding of national and foreign doctors’ location appears to be needed to design more effective policies to reduce the imbalance of medical services across geographical areas.The study was supported by a research grant from the Portuguese High Commission for Health to the International Health Department of the Institute of Hygiene and Tropical. Medicine

Development and validation of a rabbit model of Pseudomonas aeruginosa non-ventilated pneumonia for preclinical drug development

BackgroundNew drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections.MethodsWe report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression.ResultsIn a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased &gt;100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO2 &lt;60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P&lt;0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T&gt;MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved Cmax/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects.ConclusionThe rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia

Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola

<p>Abstract</p> <p>Background</p> <p>Malaria is the infectious disease causing the highest morbidity and mortality in Angola and due to widespread chloroquine (CQ) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from CQ to artemisinin combination therapies (ACT) in adults, and sulphadoxine/pyrimethamine (S/P) in pregnant women. Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P.</p> <p>Methods</p> <p>Blood samples were collected from 245 children with uncomplicated malaria, admitted at the Pediatric Hospital Dr. David Bernardino (HPDB), Angola, and the occurrence of mutations in <it>Plasmodium falciparum </it>was investigated in the <it>pfmdr1 </it>(N86Y) and <it>pfcrt </it>(K76T) genes, associated with CQ resistance, as well as in <it>pfdhfr </it>(C59R) and <it>pfdhps </it>(K540E), conferring SP resistance.</p> <p>Results</p> <p>The frequencies of <it>pfmdr1 </it>mutations in codon 86 were 28.6% N, 61.3% Y and 10.1% mixed infections (NY). The frequency of <it>pfcrt </it>mutations in codon 76 were 93.9% K, 5.7% T and 0.4% mixed infections (KT). For <it>pfdhfr </it>the results were in codon 59, 60.6% C, 20.6% R and 18.8% mixed infections (CR). Concerning <it>pfdhps</it>, 6.3% of the isolates were bearers of the mutation 540E and 5.4% mixed infections (K540E).</p> <p>Conclusion</p> <p>The results of this epidemiologic study showed high presence of CQ resistance markers while for SP a much lower prevalence was detected for the markers under study.</p