Search

Purpose To compare bacteria recovered by standard cultures and metataxonomics, particularly with regard to ventilator-associated pneumonia (VAP) pathogens, and to determine if the presence of particular bacteria or microbiota in tracheal and oropharyngeal secretions during the course of intubation was associated with the development of VAP. Methods In this case–control study, oropharyngeal secretions and endotracheal aspirate were collected daily in mechanically ventilated patients. Culture and metataxonomics (16S rRNA gene-based taxonomic profiling of bacterial communities) were performed on serial upper respiratory samples from patients with late-onset definite VAP and their respective controls. Results Metataxonomic analyses showed that a low relative abundance of Bacilli at the time of intubation in the oropharyngeal secretions was strongly associated with the subsequent development of VAP. On the day of VAP, the quantity of human and bacterial DNA in both tracheal and oropharyngeal secretions was significantly higher in patients with VAP than in matched controls with similar ventilation times. Molecular techniques identified the pathogen(s) of VAP found by culture, but also many more bacteria, classically difficult to culture, such as Mycoplasma spp. and anaerobes. Conclusions Molecular analyses of respiratory specimens identified markers associated with the development of VAP, as well as important differences in the taxa abundance between VAP and controls. Further prospective trials are needed to test the predictive value of these markers, as well as the relevance of uncultured bacteria in the pathogenesis of VAP. Electronic supplementary material The online version of this article (10.1007/s00134-019-05660-8) contains supplementary material, which is available to authorized users.

Low-dose steroids have shown contradictory results in trials and three recent meta-analyses. We aimed to assess the efficacy and safety of low-dose steroids for severe sepsis and septic shock by Bayesian methodology.Randomized trials from three published meta-analyses were reviewed and entered in both classic and Bayesian databases to estimate relative risk reduction (RRR) for 28-day mortality, and relative risk increase (RRI) for shock reversal and side effects.In septic shock trials only (Marik meta-analysis; N = 965), the probability that low-dose steroids decrease mortality by more than 15% (i.e., RRR15%) was 0.41 (0.24 for RRR20% and 0.14 for RRR25%). For severe sepsis and septic shock trials combined, the results were as follows: (1) for the Annane meta-analysis (N = 1,228), the probabilities were 0.57 (RRR15%), 0.32 (RRR20%), and 0.13 (RRR25%); (2) for the Minneci meta-analysis (N = 1,171), the probability was 0.57 to achieve mortality RRR15%, 0.32 (RRR20%), and 0.14 (RRR25%). The removal of the Sprung trial from each analysis did not change the overall results. The probability of achieving shock reversal ranged from 65 to 92%. The probability of developing steroid-induced side effects was as follows: for gastrointestinal bleeding (N = 924), there was a 0.73 probability of steroids causing an RRI1%, 0.70 for RRI2%, and 0.67 for RRI5%; for superinfections (N = 964), probabilities were 0.81 (RRI1%), 0.76 (RRI2%), and 0.70 (RRI5%); and for hyperglycemia (N = 540), 0.99 (RRI1%), 0.97 (RRI2%), and 0.94 (RRI5%).Based on clinically meaningful thresholds (RRR15-25%) for mortality reduction in severe sepsis or septic shock, the Bayesian approach to all three meta-analyses consistently showed that low-dose steroids were not associated with survival benefits. The probabilities of developing steroid-induced side effects (superinfections, bleeding, and hyperglycemia) were high for all analyses.

Controversies concerning the pivotal trial and negative results from other Drotrecogin alfa activated (DAA) trials have raised questions about its efficacy in severe sepsis patients. Based on all available evidence, our study aimed to respond to: (1) What is the current probability that DAA is not better than the control? If the current probability is not small, e.g. greater than 0.05, then (2) How many patients will be needed for the DAA confirmatory trial?We applied the Bayesian methodology to all randomized trials which tested anti-thrombotic therapies for severe sepsis. Prior distributions were defined as severe skeptic (all anti-thrombotic trials or DAA trials); moderate skeptic (anti-thrombotic trials with high risk of death); mild skeptic (DAA trials only); enthusiastic (DAA trials with high risk of death).The total study sample includes 7,683 patients: DAA (N = 3,143); Anti-thrombin-III (N = 2,581); tissue factor pathway inhibitor (N = 1,959). Answer 1: All current probabilities that DAA is not better than the control (except for the enthusiastic analysis) range from 0.14 to 0.48, which strongly suggest the need for a confirmatory trial. Answer 2: The number of patients necessary for the DAA confirmatory trial ranges up to 8,350 for the severe skeptic; 730-810 for moderate skeptic; 550-685 for mild skeptic; and zero for enthusiastic analysis.A confirmatory trial with approximately 600 patients with severe sepsis and high risk of death can provide a convincing answer for both the mild and moderate skeptic physicians concerning the efficacy of DAA in severe sepsis.