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1.
Crit Care ; 27(1): 150, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-37076881

RESUMO

BACKGROUND: ICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare. METHODS: We performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days. RESULTS: Within the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70-0.78]), junior physicians (0.78 [0.74-0.81]) and attending physicians (0.75 [0.72-0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67-0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death. CONCLUSIONS: Subjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing. Trial registration ISRCTN ISRCTN59376582 , retrospectively registered October 31st 2013.


Assuntos
Estado Terminal , Respiração Artificial , Humanos , Estado Terminal/terapia , Estudos Prospectivos , Modelos Teóricos , Medição de Risco
2.
Crit Care ; 26(1): 355, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380312

RESUMO

BACKGROUND: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. METHODS: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. RESULTS: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: - 23.7%; 80% confidence interval [CI] - 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) µg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 µg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. CONCLUSIONS: The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016.


Assuntos
Pneumonia Associada à Ventilação Mecânica , Infecções por Pseudomonas , Animais , Humanos , Adolescente , Pseudomonas aeruginosa , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/prevenção & controle , Respiração Artificial/efeitos adversos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Método Duplo-Cego , Unidades de Terapia Intensiva , Anticorpos Monoclonais/uso terapêutico , Resultado do Tratamento
3.
Semin Respir Crit Care Med ; 43(2): 310-318, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35100650

RESUMO

Among the viruses possibly responsible for hospital-acquired and ventilator-associated pneumonia, herpes simplex virus (HSV) is probably the most often involved: HSV reactivation is frequent in intensive care unit patients, and lung parenchymal infection (HSV bronchopneumonitis) has been well described, either using cytological signs of parenchymal involvement in cells obtained during bronchoalveolar lavage or using HSV virus load in the lower respiratory tract. Although treating patients with HSV bronchopneumonitis may be recommended, based on expert opinion, prophylactic or preemptive treatment of HSV reactivation should be avoided. Ventilator-associated pneumonia due to cytomegalovirus (CMV) is less frequent than HSV bronchopneumonitis, and more difficult to diagnose. No data exists on the impact of antiviral treatment on CMV pneumonia. The involvement of respiratory viruses has been described in patients with healthcare-associated pneumonia and hospital-acquired pneumonia, but their role in ventilator-associated pneumonia is not clear.


Assuntos
Infecções por Citomegalovirus , Herpes Simples , Infecções por Herpesviridae , Pneumonia Associada à Ventilação Mecânica , Pneumonia Viral , Herpes Simples/diagnóstico , Hospitais , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Simplexvirus
4.
Age Ageing ; 50(5): 1546-1556, 2021 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-33993243

RESUMO

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.


Assuntos
Unidades de Terapia Intensiva , Pró-Calcitonina , Idoso , Algoritmos , Antibacterianos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Clin Chem Lab Med ; 59(2): 441-453, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32986609

RESUMO

Objectives: Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. Methods: We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality. Results: Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5-7.6 days; adjusted difference in days -2.01 [95% CI, -2.45 to -1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI -3.59 to -1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05). Conclusions: This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.


Assuntos
Antibacterianos/uso terapêutico , Biomarcadores/sangue , Mortalidade/etnologia , Pró-Calcitonina/sangue , Insuficiência Renal Crônica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Gestão de Antimicrobianos , Uso de Medicamentos , Feminino , Hospitalização , Humanos , Rim , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Clin Infect Dis ; 69(3): 388-396, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30358811

RESUMO

BACKGROUND: Whether procalcitonin (PCT)-guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of PCT-guided antibiotic management in patients with bacteremia. METHODS: We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days. RESULTS: Mean duration of antibiotic therapy was significantly shorter for 253 patients who received PCT-guided treatment than for 270 control patients (-2.86 days [95% confidence interval [CI], -4.88 to -.84]; P = .006). Mortality was similar in both arms (16.6% vs 20.0%; P = .263). In subgroup analyses by type of pathogen, we noted a trend of shorter mean antibiotic durations in the PCT arm for patients infected with gram-positive organisms or Escherichia coli and significantly shorter treatment for subjects with pneumococcal bacteremia. In analysis by site of infection, antibiotic exposure was shortened in PCT subjects with Streptococcus pneumoniae respiratory infection and those with E. coli urogenital infections. CONCLUSIONS: This meta-analysis of patients with bacteremia receiving PCT-guided antibiotic management demonstrates lower antibiotic exposure without an apparent increase in mortality. Few differences were demonstrated in subgroup analysis stratified by type or site of infection but notable for decreased exposure in patients with pneumococcal pneumonia and E. coli urogenital infections.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Pró-Calcitonina/sangue , Gestão de Antimicrobianos/métodos , Bacteriemia/mortalidade , Biomarcadores/sangue , Hemocultura , Gerenciamento Clínico , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Unidades de Terapia Intensiva , Infecções Pneumocócicas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Streptococcus pneumoniae/efeitos dos fármacos
7.
Clin Infect Dis ; 69(11): 1912-1918, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30722013

RESUMO

BACKGROUND: Randomized clinical trials (RCTs) in hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively) are important for the evaluation of new antimicrobials. However, the heterogeneity in endpoints used in RCTs evaluating treatment of HABP/VABP may puzzle clinicians. The aim of this work was to reach a consensus on clinical endpoints to consider in future clinical trials evaluating antimicrobial treatment efficacy for HABP/VABP. METHODS: Twenty-six international experts from intensive care, infectious diseases, and the pharmaceutical industry were polled using the Delphi method. RESULTS: The panel recommended a hierarchical composite endpoint including, by priority order, (1) survival at day 28, (2) mechanical ventilation-free days through day 28, and (3) clinical cure between study days 7 and 10 for VABP; and (1) survival (day 28) and (2) clinical cure (days 7-10) for HABP. Clinical cure was defined as the combination of resolution of signs and symptoms present at enrollment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and mechanical ventilation-free days though day 28, and clinical cure between day 7 and day 10 after treatment initiation. Finally, the hierarchical order of endpoint components was reached after 3 Delphi rounds (72% agreement). CONCLUSIONS: We provide a multinational expert consensus on separate hierarchical composite endpoints for VABP and HABP, and on a definition of clinical cure that could be considered for use in future HABP/VABP clinical trials.


Assuntos
Antibacterianos/uso terapêutico , Pneumonia Bacteriana/microbiologia , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Consenso , Cuidados Críticos/métodos , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Humanos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-29038277

RESUMO

Ventilator-associated bacterial pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent guidelines of the Infectious Diseases Society of America and the American Thoracic Society recommend a 7-day therapeutic course for VABP based on the balance of no negative impact on all-cause mortality, less resistance emergence, and fewer antibiotic treatment days, counterbalanced with a higher relapse rate for patients whose pathogen is a nonfermenter. The bacterial burden causing an infection has a substantial impact on treatment outcome and resistance selection. We describe the baseline bronchoalveolar lavage (BAL) fluid burden of organisms in suspected VABP patients screened for inclusion in a clinical trial. We measured the urea concentrations in plasma and BAL fluid to provide an index of the dilution of the bacterial and drug concentrations in the lung epithelial lining fluid introduced by the BAL procedure. We were then able to calculate the true bacterial burden as the diluted colony count times the dilution factor. The median dilution factor was 28.7, with the interquartile range (IQR) being 11.9 to 53.2. Median dilution factor-corrected colony counts were 6.18 log10(CFU/ml) [IQR, 5.43 to 6.46 log10(CFU/ml)]. In a subset of patients, repeat BAL on day 5 showed a good stability of the dilution factor. We previously showed that large bacterial burdens reduce or stop bacterial killing by granulocytes. (This study has been registered at ClinicalTrials.gov under registration no. NCT01570192.).


Assuntos
Técnicas Bacteriológicas/métodos , Líquido da Lavagem Broncoalveolar/microbiologia , Pneumonia Bacteriana/microbiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Ureia/análise , Carga Bacteriana , Humanos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Ureia/sangue
9.
Curr Opin Crit Care ; 24(5): 332-338, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30036192

RESUMO

PURPOSE OF REVIEW: Successful treatment of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remains a difficult and complex undertaking. Better knowledge of the pathogens involved in that setting may allow reassessment of our current modalities of therapy and definition of better protocols. RECENT FINDINGS: Microorganisms responsible for HAP/VAP differ according to geographic areas, ICU patients' specific characteristics, durations of hospital and ICU stays before onset of the disease, and risk factors for MDR pathogens. However, a number of studies have shown that Gram-negative bacilli (GNB) - particularly Pseudomonas aeruginosa and Enterobacteriaceae - cause many of the respiratory infections in this setting, with minimal differences between HAP and VAP, indicating that the cause depends more on the underlying clinical condition of patients rather than previous intubation. SUMMARY: When selecting initial antimicrobial therapy in patients with HAP/VAP, more attention should be paid to individual risk factors for MDR pathogens, severity of the clinical situation, and the local epidemiology than to the type of pneumonia.


Assuntos
Antibacterianos/uso terapêutico , Bactérias Aeróbias Gram-Negativas/patogenicidade , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Unidades de Terapia Intensiva , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Pneumonia Associada a Assistência à Saúde/epidemiologia , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Medição de Risco
10.
Crit Care ; 22(1): 191, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111341

RESUMO

BACKGROUND: The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection. METHODS: For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the "procalcitonin-guided" group) or the current standard of care (the "controls"). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay. RESULTS: Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p <  0.001). CONCLUSION: Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.


Assuntos
Antibacterianos/administração & dosagem , Avaliação de Resultados da Assistência ao Paciente , Pró-Calcitonina/análise , Sepse/tratamento farmacológico , Antibacterianos/uso terapêutico , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Escores de Disfunção Orgânica , Pró-Calcitonina/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/sangue
11.
Am J Respir Crit Care Med ; 196(4): 447-457, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28103448

RESUMO

RATIONALE: Optimal positive end-expiratory pressure (PEEP) is unknown in patients with severe acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation receiving mechanical ventilation with very low tidal volume. OBJECTIVES: To evaluate the ability of electrical impedance tomography (EIT) to monitor a PEEP trial and to derive from EIT the best compromise PEEP in this setting. METHODS: A decremental PEEP trial (20-0 cm H2O) in 5 cm H2O steps was monitored by EIT, with lung images divided into four ventral-to-dorsal horizontal regions of interest. The EIT-based PEEP providing the best compromise between overdistention and collapsed zones was arbitrarily defined as the lowest pressure able to limit EIT-assessed collapse to less than or equal to 15% with the least overdistention. Driving pressure was maintained constant at 14 cm H2O in pressure controlled mode. MEASUREMENTS AND MAIN RESULTS: Tidal volume, static compliance, tidal impedance variation, end-expiratory lung impedance, and their respective regional distributions were visualized at each PEEP level in 15 patients on extracorporeal membrane oxygenation. Low tidal volume (2.9-4 ml/kg ideal body weight) and poor compliance (12.1-18.7 ml/cm H2O) were noted, with significantly higher tidal volume and compliance at PEEP10 and PEEP5 than PEEP20. EIT-based best compromise PEEPs were 15, 10, and 5 cm H2O for seven, six, and two patients, respectively, whereas PEEP20 and PEEP0 were never selected. CONCLUSIONS: The broad variability in optimal PEEP observed in these patients with severe ARDS under extracorporeal membrane oxygenation reinforces the need for personalized titration of ventilation settings. EIT may be an interesting noninvasive bedside tool to provide real-time monitoring of the PEEP impact in these patients.


Assuntos
Impedância Elétrica , Oxigenação por Membrana Extracorpórea/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/terapia , Tomografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Reprodutibilidade dos Testes , Síndrome do Desconforto Respiratório/fisiopatologia , Volume de Ventilação Pulmonar , Adulto Jovem
12.
Eur Respir J ; 50(3)2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28890434

RESUMO

The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent.The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited.A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink).Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population-intervention-comparison-outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.


Assuntos
Cuidados Críticos/normas , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Pneumonia Associada à Ventilação Mecânica/terapia , Gerenciamento Clínico , Europa (Continente) , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sociedades Médicas
13.
Crit Care Med ; 45(8): 1359-1366, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28471885

RESUMO

OBJECTIVE: Long-term outcomes of patients treated with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure (i.e., cardiogenic shock complicating chronic cardiomyopathy) have not yet been reported. This study was undertaken to describe their outcomes and determine mortality-associated factors. DESIGN: Retrospective analysis of data prospectively collected. SETTING: Twenty-six-bed tertiary hospital ICU. PATIENTS: One hundred five patients implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: From March 2007 to January 2015, 105 patients were implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure in our ICU (67% of them had an intraaortic balloon pump to unload the left ventricle). Their 1-year survival rate was 42%; most of the survivors were transplanted either directly or after switching to central bilateral centrifugal pump, ventricular-assist device, or total artificial heart. Most deaths occurred early after multiple organ failure. Multivariable analyses retained (odds ratio [95% CI]) pre-extracorporeal membrane oxygenation Sequential Organ Failure Assessment score of more than 11 (3.3 [1.3-8.3]), idiopathic cardiomyopathy (0.4 [0.2-1]), cardiac disease duration greater than 2 years pre-extracorporeal membrane oxygenation (2.8 [1.2-6.9]), and pre-extracorporeal membrane oxygenation blood lactate greater than 4 mmol/L (2.6 [1.03-6.4]) as independent predictors of 1-year mortality. Only 17% of patients with pre-extracorporeal membrane oxygenation Sequential Organ Failure Assessment scores of 14 or more survived, whereas 52% of those with scores less than 7 and 60% of those with scores 7 or more and less than 11 were alive 1 year later. CONCLUSIONS: Among this selected cohort of 105 patients implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure, 1-year survival was 42%, but better for patients with pre-extracorporeal membrane oxygenation Sequential Organ Failure Assessment scores of less than 11. Venoarterial-extracorporeal membrane oxygenation should be considered for patients with acute decompensated heart failure, but timing of implantation is crucial.


Assuntos
Cardiomiopatias/terapia , Oxigenação por Membrana Extracorpórea/métodos , Insuficiência Cardíaca/terapia , Choque Cardiogênico/terapia , Adulto , Idoso , Cardiomiopatias/mortalidade , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Estudos Retrospectivos , Fatores de Risco , Choque Cardiogênico/mortalidade , Centros de Atenção Terciária
14.
Anesthesiology ; 126(5): 890-908, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28248714

RESUMO

BACKGROUND: Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. METHODS: A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. RESULTS: Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. CONCLUSIONS: Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.


Assuntos
Antibacterianos/administração & dosagem , Nebulizadores e Vaporizadores , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Respiração Artificial/efeitos adversos , Antibacterianos/uso terapêutico , Estado Terminal , Humanos , Unidades de Terapia Intensiva
15.
Crit Care ; 21(1): 76, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28347320

RESUMO

BACKGROUND: Despite quick implementation of reperfusion therapies, a few patients with high-risk, acute, massive, pulmonary embolism (PE) remain highly hemodynamically unstable. Others have absolute contraindication to receive reperfusion therapies. Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) might lower their right ventricular overload, improve hemodynamic status, and restore tissue oxygenation. METHODS: ECMO-related complications and 90-day mortality were analyzed for 17 highly unstable, ECMO-treated, massive PE patients admitted to a tertiary-care center (2006-2015). Hospital- discharge survivors were assessed for long-term health-related quality of life. A systematic review of this topic was also conducted. RESULTS: Seventeen high-risk PE patients [median age 51 (range 18-70) years, Simplified Acute Physiology Score II (SAPS II) 78 (45-95)] were placed on VA-ECMO for 4 (1-12) days. Among 15 (82%) patients with pre-ECMO cardiac arrest, seven (41%) were cannulated during cardiopulmonary resuscitation, and eight (47%) underwent pre-ECMO thrombolysis. Pre-ECMO median blood pressure, pH, and blood lactate were, respectively: 42 (0-106) mmHg, 6.99 (6.54-7.37) and 13 (4-19) mmol/L. Ninety-day survival was 47%. Fifteen (88%) patients suffered in-ICU severe hemorrhages with no impact on survival. Like other ECMO-treated patients, ours reported limitations of all physical domains but preserved mental health 19 (4-69) months post-ICU discharge. CONCLUSIONS: VA-ECMO could be a lifesaving rescue therapy for patients with high-risk, acute, massive PE when thrombolytic therapy fails or the patient is too sick to benefit from surgical thrombectomy. Because heparin-induced clot dissolution and spontaneous fibrinolysis allows ECMO weaning within several days, future studies should investigate whether VA-ECMO should be the sole therapy or completed by additional mechanical clot-removal therapies in this setting.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Embolia Pulmonar/mortalidade , Embolia Pulmonar/terapia , Adolescente , Adulto , Idoso , Oxigenação por Membrana Extracorpórea/mortalidade , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Paris , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Análise de Sobrevida , Sobreviventes/estatística & dados numéricos , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos
16.
Semin Respir Crit Care Med ; 38(3): 346-358, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28578557

RESUMO

Morbidity, mortality, and economic burden of nosocomial pneumonia caused by Staphylococcus aureus and Pseudomonas aeruginosa remain high in mechanically ventilated and hospitalized patients despite the use of empirical antibiotic therapy or antibiotics against specific classes of pathogens and procedures to reduce nosocomial infections in hospital settings. Newer agents that neutralize or inhibit specific S. aureus or P. aeruginosa virulence factors may eliminate or reduce the risk for developing pneumonia before or during mechanical ventilation and may improve patient outcomes through mechanisms that differ from those of antibiotics. In this article, we review the types, mechanisms of action, potential advantages, and stage of development of antivirulence agents (AVAs) that hold promise as alternative preventive or interventional therapies against S. aureus­ and P. aeruginosa­associated nosocomial pneumonias. We also present and discuss challenges to the effective utilization of AVAs separately from or in addition to antibiotics and the design of clinical trials and meaningful study end points.


Assuntos
Antibacterianos/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Fatores de Virulência/antagonistas & inibidores , Anticorpos Monoclonais/farmacologia , Toxinas Bacterianas/metabolismo , Bacteriófagos/metabolismo , Biofilmes/efeitos dos fármacos , Infecção Hospitalar/tratamento farmacológico , Citotoxinas/farmacologia , Farmacorresistência Bacteriana Múltipla , Humanos , Leucocidinas/farmacologia , Microbiota/fisiologia , Pneumonia/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pseudomonas aeruginosa , Percepção de Quorum/efeitos dos fármacos , Staphylococcus aureus
17.
Cochrane Database Syst Rev ; 10: CD007498, 2017 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-29025194

RESUMO

BACKGROUND: Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. OBJECTIVES: The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. SELECTION CRITERIA: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS: Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis. MAIN RESULTS: From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidance was associated with a 2.4-day reduction in antibiotic exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI 0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay were similar in both groups. A sensitivity aggregate-data analysis based on all 32 eligible trials showed similar results. AUTHORS' CONCLUSIONS: This updated meta-analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects. Results were similar for different clinical settings and types of ARIs, thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs. Future high-quality research is needed to confirm the results in immunosuppressed patients and patients with non-respiratory infections.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Calcitonina/sangue , Precursores de Proteínas/sangue , Infecções Respiratórias/tratamento farmacológico , Doença Aguda , Antibacterianos/efeitos adversos , Infecções Bacterianas/sangue , Infecções Bacterianas/mortalidade , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Causas de Morte , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/sangue , Infecções Respiratórias/mortalidade , Falha de Tratamento
18.
19.
J Antimicrob Chemother ; 71(9): 2534-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27272723

RESUMO

OBJECTIVES: This study was designed to evaluate the pharmacodynamics of doripenem, imipenem and meropenem as a predictor of clinical success, mortality, 28 day recurrence and development of resistance in patients treated for Pseudomonas aeruginosa ventilator-associated pneumonia (VAP). PATIENTS AND METHODS: Previously published demographic and outcome data derived from patients treated for P. aeruginosa VAP with doripenem, imipenem or meropenem were utilized. Patient-specific data were used in conjunction with published population pharmacokinetic models to construct concentration-time profiles for each patient. Etest MICs were used to determine pharmacodynamic profiles. Classification and regression tree (CART) analysis was utilized to partition pharmacodynamics based on outcomes with P values of 0.05. RESULTS: Eighty-six patients were included in the analysis. Initial carbapenem MICs ranged from 0.03 to 32 mg/L. VAP recurred in 28 patients; of these, 17 patients were initially infected with susceptible organisms, and 14 of them developed resistance. CART fT>MIC partitions identified for clinical success and survival were 19.2% (P = 0.016) and 47.9% (P < 0.001), respectively. No statistically significant partitions for fT>MIC were identified for recurrence or resistance development. CONCLUSIONS: We identified fT>MIC cut-offs for positive clinical outcomes in patients with P. aeruginosa VAP that were similar to those observed in animal models of infection for stasis (∼20%) and 1 log decreases in cfu (∼40%). Although in vitro studies have suggested a link between drug exposure and development of resistance, we were unable to identify such a relationship clinically.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Carbapenêmicos/farmacologia , Carbapenêmicos/farmacocinética , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/administração & dosagem , Carbapenêmicos/administração & dosagem , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Doripenem , Feminino , Humanos , Imipenem/administração & dosagem , Imipenem/farmacocinética , Imipenem/farmacologia , Masculino , Meropeném , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Tienamicinas/administração & dosagem , Tienamicinas/farmacocinética , Tienamicinas/farmacologia , Resultado do Tratamento
20.
Crit Care ; 20(1): 136, 2016 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-27329228

RESUMO

The rapid emergence and dissemination of antibiotic-resistant microorganisms in ICUs worldwide threaten adequate antibiotic coverage of infected patients in this environment. The causes of this problem are multifactorial, but the core issues are clear: the emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Because a significant increase in mortality is observed when antibiotic therapy is delayed in infected ICU patients, initial therapy should be broad enough to cover all likely pathogens. Receipt of unnecessary prolonged broad-spectrum antibiotics, however, should be avoided. Local microbiologic data are extremely important to predict the type of resistance that may be present for specific causative bacteria, as is prior antibiotic exposure, and antibiotic choices should thus be made at an individual patient level.


Assuntos
Antibacterianos/farmacocinética , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Antibacterianos/uso terapêutico , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Bactérias/patogenicidade , Saúde Global/tendências , Humanos , Unidades de Terapia Intensiva/organização & administração
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