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      Update on ventilator-associated pneumonia

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          Abstract

          Ventilator-associated pneumonia (VAP) is the most frequent life-threatening nosocomial infection in intensive care units. The diagnostic is difficult because radiological and clinical signs are inaccurate and could be associated with various respiratory diseases. The concept of infection-related ventilator-associated complication has been proposed as a surrogate of VAP to be used as a benchmark indicator of quality of care. Indeed, bundles of prevention measures are effective in decreasing the VAP rate. In case of VAP suspicion, respiratory secretions must be collected for bacteriological secretions before any new antimicrobials. Quantitative distal bacteriological exams may be preferable for a more reliable diagnosis and therefore a more appropriate use antimicrobials. To improve the prognosis, the treatment should be adequate as soon as possible but should avoid unnecessary broad-spectrum antimicrobials to limit antibiotic selection pressure. For empiric treatments, the selection of antimicrobials should consider the local prevalence of microorganisms along with their associated susceptibility profiles. Critically ill patients require high dosages of antimicrobials and more specifically continuous or prolonged infusions for beta-lactams. After patient stabilization, antimicrobials should be maintained for 7–8 days. The evaluation of VAP treatment based on 28-day mortality is being challenged by regulatory agencies, which are working on alternative surrogate endpoints and on trial design optimization.

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          Most cited references90

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          Clinical and economic consequences of ventilator-associated pneumonia: a systematic review.

          Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in critically ill patients. The clinical and economic consequences of VAP are unclear, with a broad range of values reported in the literature To perform a systematic review to determine the incidence of VAP and its attributable mortality rate, length of stay, and costs. Computerized PUBMED and MEDLINE search supplemented by manual searches for relevant articles, limited to articles published after 1990. English-language observational studies and randomized trials that provided data on the incidence of VAP were included. Matched cohort studies were included for calculation of attributable mortality rate and length of stay. Data were extracted on patient population, diagnostic criteria for VAP, incidence, outcome, type of intensive care unit, and study design. The cumulative incidence of VAP was calculated by combining the results of several studies using standard formulas for combining proportions, in which the weighted average and variance are calculated. Results from studies comparing intensive care unit and hospital mortality due to VAP, additional length of stay, and additional days of mechanical ventilation were pooled using a random effects model, with assessment of heterogeneity. Our findings indicate a) between 10% and 20% of patients receiving >48 hrs of mechanical ventilation will develop VAP; b) critically ill patients who develop VAP appear to be twice as likely to die compared with similar patients without VAP (pooled odds ratio, 2.03; 95% confidence interval, 1.16-3.56); c) patients with VAP have significantly longer intensive care unit lengths of stay (mean = 6.10 days; 95% confidence interval, 5.32-6.87 days); and d) patients who develop VAP incur > or = USD $10,019 in additional hospital costs. Ventilator-associated pneumonia occurs in a considerable proportion of patients undergoing mechanical ventilation and is associated with substantial morbidity, a two-fold mortality rate, and excess cost. Given these findings, strategies that effectively prevent VAP are urgently needed.
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            Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.

            Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia. This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated. Of 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.
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              Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections.

              The objective of this study was to evaluate the relationship of the predicted pharmacodynamic parameters 24-h area under the inhibitory curve (AUIC=area under the concentration-time curve for 24h of dosing/minimum inhibitory concentration (AUC0-24/MIC) and time above the minimum inhibitory concentration (T>MIC) with clinical and microbiological outcomes in patients with bacteraemia and sepsis treated with cefepime or ceftazidime. Pharmacokinetic and pharmacodynamic parameters were derived for 76 of 107 patients enrolled in two prospective, randomised, clinical trials comparing cefepime with ceftazidime for the treatment of sepsis with bacteraemia, lower respiratory tract infection or complicated urinary tract infection. The relationships between the pharmacodynamic parameters and outcomes were examined. Whilst no significant differences in clinical outcomes were observed between cefepime and ceftazidime, there were significant differences in the pharmacodynamic analysis. Patients with an AUIC> or =250 had significantly greater clinical cure (79% vs. 33%; P=0.002) and bacteriological eradication (96% vs. 44%; P MIC of 100% had significantly greater clinical cure (82% vs. 33%; P=0.002) and bacteriological eradication (97% vs. 44%; P MIC of MIC was <100%.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: SupervisionRole: ValidationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ResourcesRole: Writing – Original Draft Preparation
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: SupervisionRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                29 November 2017
                2017
                : 6
                : 2061
                Affiliations
                [1 ]IAME, Inserm U1137, Paris Diderot University, Paris, F75018, France
                [2 ]Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat University Hospital, Paris, France
                Author notes

                Competing interests: J-FT gave lectures for Merck, Pfizer, and Gilead on antimicrobial therapy and participated in scientific boards of Paratek, Bayer, Merck, and 3M. The other authors declare that they have no competing interests.

                Author information
                https://orcid.org/0000-0002-6063-7383
                Article
                10.12688/f1000research.12222.1
                5710313
                29225790
                a58f96a0-a8c1-48f3-a1ca-3edcaf8656ab
                Copyright: © 2017 Timsit JF et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 November 2017
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles
                Bacterial Infections
                Nosocomial & Healthcare-Associated Infections
                Respiratory Problems in Critical Care

                ventilator-associated pneumonia,vap,nosocomial infection,antimicrobials

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