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Goncalves-Pereira J.,Polyvalent Intensive Care Unit
Critical care (London, England) | Year: 2011

Several reports have shown marked heterogeneity of antibiotic pharmacokinetics (PK) in patients admitted to ICUs, which might potentially affect outcomes. Therefore, the pharmacodynamic (PD) parameter of the efficacy of β-lactam antibiotics, that is, the time that its concentration is above the bacteria minimal inhibitory concentration (T > MIC), cannot be safely extrapolated from data derived from the PK of healthy volunteers. We performed a full review of published studies addressing the PK of intravenous β-lactam antibiotics given to infected ICU patients. Study selection comprised a comprehensive bibliographic search of the PubMed database and bibliographic references in relevant reviews from January 1966 to December 2010. We selected only English-language articles reporting studies addressing β-lactam antibiotics that had been described in at least five previously published studies. Studies of the PK of patients undergoing renal replacement therapy were excluded. A total of 57 studies addressing six different β-lactam antibiotics (meropenem, imipenem, piperacillin, cefpirome, cefepime and ceftazidime) were selected. Significant PK heterogeneity was noted, with a broad, more than twofold variation both of volume of distribution and of drug clearance (Cl). The correlation of antibiotic Cl with creatinine clearance was usually reported. Consequently, in ICU patients, β-lactam antibiotic half-life and T > MIC were virtually unpredictable, especially in those patients with normal renal function. A better PD profile was usually obtained by prolonged or even continuous infusion. Tissue penetration was also found to be compromised in critically ill patients with septic shock. The PK of β-lactam antibiotics are heterogeneous and largely unpredictable in ICU patients. Consequently, the dosing of antibiotics should be supported by PK concepts, including data derived from studies of the PK of ICU patients and therapeutic drug monitoring. Source

Goncalves-Pereira J.,Polyvalent Intensive Care Unit | Paiva J.-A.,University of Porto
Journal of Critical Care | Year: 2013

Considerable evidence has shown that adequate antibiotic therapy is of utmost importance in the critically ill septic patient. However, antibiotic concentration may be insufficient early in infection course. We propose the concept of dose modulation, meaning front-line variability of antibiotic dose, according to patient and microorganism characteristics, followed by its reduction after clinical response and patient recovery. Therefore, dose modulation means concentrating the largest weight of antibiotics at the front-end, when the microbial load is higher and the pharmacokinetic changes poses the highest risk of underdosing and nibbling off antibiotic dose, when the sepsis syndrome is improving, guided by pharmacokinetic and pharmacodynamic data. © 2013 Elsevier Inc. Source

Povoa P.,Polyvalent Intensive Care Unit | Povoa P.,New University of Lisbon | Salluh J.I.F.,DOr Institute for Research and Education | Salluh J.I.F.,Instituto Nacional Of Cancer
Annals of Intensive Care | Year: 2012

Biomarkers of infection, namely C-reactive protein and procalcitonin (PCT), are potentially useful in the diagnosis of infection as well as in the assessment of its response to antibiotic therapy. C-reactive protein variations overtime appears to have a good performance for the diagnosis of infection. Procalcitonin shows a better correlation with clinical severity. In addition, to overcome the worldwide problem of antibiotic overuse as well as misuse, biomarker guidance of antibiotic stewardship represents a promising new approach. In several randomized, controlled trials, including adult critically ill patients, PCT guidance was repeatedly associated with a decrease in the duration of antibiotic therapy. However, these trials present several limitations, namely high rate of patients' exclusion, high rate of algorithm overruling, long duration of antibiotic therapy in the control group, disregard the effect of renal failure on PCT level, and above all a possible higher mortality and higher late organ failure in the PCT arm. In addition, some infections (e.g., endocarditis) as well as frequent nosocomial bacteria (e.g., Pseudomonas aeruginosa) are not suitable to be assessed by PCT algorithms. Therefore, the true value of PCT-guided algorithm of antibiotic stewardship in assisting the clinical decision-making process at the bedside remains uncertain. Future studies should take into account the issues identified in the present review. © 2012 Póvoa and Salluh; licensee Springer. Source

Rodriguez A.,IISPV URV CIBERES | Povoa P.,Polyvalent Intensive Care Unit | Nseir S.,Lille University Hospital Center | Salluh J.,Institute for Research and Education Postgraduate Program | And 2 more authors.
Critical Care | Year: 2014

Introduction: Several aspects of ventilator-associated tracheobronchitis (VAT)-including diagnostic criteria, overlap with ventilator-associated pneumonia (VAP), and appropriate treatment regimens-remain poorly defined. The objectives of this study were to survey reported practices in the clinical and microbiological diagnosis of VAT and to evaluate perceptions of the impact of VAT on patient outcomes. Methods: We developed a questionnaire consisting of (a) characteristics of the respondent, the ICU, and hospital; (b) current clinical and microbiological diagnostic approach; (c) empirical antibiotic therapy; and (d) the perception of physicians regarding the clinical impact of VAT and its implications. Results: A total of 288 ICUs from 16 different countries answered the survey: 147 (51%) from the Latin American (LA) group and 141 (49%) from Spain, Portugal, and France (SPF group). The majority of respondents (n = 228; 79.2%) reported making the diagnosis of VAT based on clinical and microbiological criteria, and 40 (13.9%) by clinical criteria alone. Approximately half (50.3%) of the respondents agreed that patients should receive antibiotics for the treatment of VAT. Out of all respondents, 269 (93.4%) assume that a VAT episode increases ICU length of stay, and this perception is greater in the LA group (97.3%) than in the SPF group (89.4%, P <0.05). Half of the physicians considered that VAT increases the risk of mortality, and this perception is again greater in the LA group (58.5% versus 41.1%, P <0.05). Conclusions: Given the possible high incidence of VAT and the perception of its importance as a risk factor for VAP and mortality, a large multicenter international prospective study would be helpful to validate a consensual definition of VAT, determine its incidence, and delineate its impact on subsequent VAP occurrence. © 2014 Rodríguez et al.; licensee BioMed Central Ltd. Source

Povoa P.,Polyvalent Intensive Care Unit | Povoa P.,New University of Lisbon | Teixeira-Pinto A.M.,University of Porto | Carneiro A.H.,Abel Salazar Biomedical Sciences Institute
Critical Care | Year: 2011

Introduction: C-reactive protein (CRP) has been shown to be a valuable marker in the diagnosis of infection and in monitoring its response to antibiotics. Our objective was to evaluate serial CRP measurements after prescription of antibiotics to describe the clinical course of Community-Acquired Sepsis admitted to intensive care units (ICU).Methods: During a 12-month period a multi-center, prospective, observational study was conducted, segregating adults with Community-Acquired Sepsis. Patients were followed-up during the first five ICU days, day of ICU discharge or death and hospital outcome. CRP-ratio was calculated in relation to Day 1 CRP concentration. Patients were classified according to the pattern of CRP-ratio response to antibiotics: fast response if Day 5 CRP-ratio was < 0.4, slow response if Day 5 CRP-ratio was between 0.4 and 0.8, and no response if Day 5 CRP-ratio was > 0.8. Comparison between survivors and non-survivors was performed.Results: A total of 891 patients (age 60 ± 17 yrs, hospital mortality 38%) were studied. There were no significant differences between the CRP of survivors and non-survivors until Day 2 of antibiotic therapy. On the following three days, CRP of survivors was significantly lower (P < 0.001). After adjusting for the Simplified Acute Physiology Score II and severity of sepsis, the CRP course was significantly associated with mortality (ORCRP-ratio= 1.03, confidence interval 95%= (1.02, 1.04), P < 0.001). The hospital mortality of patients with fast response, slow response and no response patterns was 23%, 30% and 41%, respectively (P = 0.001). No responders had a significant increase on the odds of death (OR = 2.5, CI95%= (1.6, 4.0), P < 0.001) when compared with fast responders.Conclusions: Daily CRP measurements after antibiotic prescription were useful as early as Day 3 in identification of Community-Acquired Sepsis patients with poor outcome. The rate of CRP decline during the first five ICU days was markedly associated with prognosis. The identification of the pattern of CRP-ratio response was useful in the recognition of the individual clinical course. © 2011 Póvoa et al.; licensee BioMed Central Ltd. Source

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