Extended antibiotic prophylaxis after pancreatoduodenectomy reduces postoperative abdominal infection in high-risk patients: Results from a retrospective cohort study.

BACKGROUND: Preoperative biliary stenting before pancreatoduodenectomy is associated with a greater risk of bacteribilia and thus could lead to more frequent and severe surgical site infections. We hypothesized that an extended antibiotic prophylaxis could reduce the risk of surgical site infections for these high-risk patients compared with standard antibiotic prophylaxis. METHODS: All consecutive patients who underwent pancreatoduodenectomy between January 1, 2010 and December 31, 2016 were included in a tricentric retrospective cohort and classified according to the risk of surgical site infections (high or low) and the type of antibiotic prophylaxis (standard or extended). Extended antibiotic prophylaxis was defined by the use of high-rank ß-lactams >2 days after surgery. Standard antibiotic prophylaxis concerned all single dose of low-rank ß-lactams antibiotic prophylaxis. The primary outcome was postoperative surgical site infections. RESULTS: Three hundred and eight patients were included; 146 (47%) were high-risk patients, and 81 (55%) received extended antibiotic prophylaxis, mostly composed of piperacilline-tazobactam and gentamicin. There were significantly fewer surgical site infections in high-risk patients receiving extended antibiotic prophylaxis versus standard antibiotic prophylaxis (odds ratio = 0.4; 95% confidence interval, 0.2-0.8; P = .011), even after adjusting on age, sex, and duration of the surgical procedure (adjusted odds ratio = 0.3; 95% confidence interval, 0.1-0.7; P = .0071). There was no statistical difference in 28-day mortality (P = .32) or 90-day mortality (P = .13). Microorganisms identified in bile culture were more often sensitive to antibiotic prophylaxis in high-risk extended antibiotic prophylaxis group than in high-risk standard antibiotic prophylaxis group (64% versus 38%; P = .01). CONCLUSION: Extended antibiotic prophylaxis is associated with a reduced risk of surgical site infections for high-risk patients with no significant reduction on 28-day mortality. Additional studies are required to determine the optimal duration of extended antibiotic prophylaxis for these patients.

The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.

PURPOSE: Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.

Respiratory microbiome in mechanically ventilated patients: a narrative review.

The respiratory microbiome has been less explored than the gut microbiome. Despite the speculated importance of dysbiosis of the microbiome in ventilator-associated pneumonia (VAP) and acute respiratory distress syndrome (ARDS), only few studies have been performed in invasively ventilated ICU patients. And only the results of small cohorts have been published. An overlap exists between bacterial populations observed in the lower respiratory tract and the oropharyngeal tract. The bacterial microbiota is characterized by relatively abundant bacteria difficult to cultivate by standard methods. Under mechanical ventilation, a dysbiosis occurs with a drop overtime in diversity. During VAP development, lung dysbiosis is characterized by a shift towards a dominant bacterial pathogen (mostly Proteobacteria) whereas enrichment of gut-associated bacteria mainly Enterobacteriaceae is the specific feature discriminating ARDS patients. However, the role of this dysbiosis in VAP and ARDS pathogenesis is not yet fully understood. A more in-depth analysis of the interplay between bacteria, virus and fungi and a better understanding of the host-microbiome interaction could provide a more comprehensive view of the role of the microbiome in VAP and ARDS pathogenesis. Priority should be given to validate a consensual and robust methodology for respiratory microbiome research and to conduct longitudinal studies. A deeper understanding of microbial interplay should be a valuable guide for care of ARDS and VAP preventive/therapeutic strategies. We present a review on the current knowledge and expose perspectives and potential clinical applications of respiratory microbiome research in mechanically ventilated patients.

Lung Microbiome in Critically Ill Patients.

The historical hypothesis of sterility of the lungs was invalidated over a decade ago when studies demonstrated the existence of sparse but very diverse bacterial populations in the normal lung and the association between pulmonary dysbiosis and chronic respiratory diseases. Under mechanical ventilation, dysbiosis occurs rapidly with a gradual decline in diversity over time and the progressive predominance of a bacterial pathogen (mainly Proteobacteria) when lung infection occurs. During acute respiratory distress syndrome, an enrichment in bacteria of intestinal origin, mainly Enterobacteriaceae, is observed. However, the role of this dysbiosis in the pathogenesis of ventilator-associated pneumonia and acute respiratory distress syndrome is not yet fully understood. The lack of exploration of other microbial populations, viruses (eukaryotes and prokaryotes) and fungi is a key issue. Further analysis of the interaction between these microbial kingdoms and a better understanding of the host-microbiome interaction are necessary to fully elucidate the role of the microbiome in the pathogenicity of acute diseases. The validation of a consensual and robust methodology in order to make the comparison of the different studies relevant is also required. Filling these different gaps should help develop preventive and therapeutic strategies for both acute respiratory distress syndrome and ventilator-associated pneumonia.

Risk factors and events in the adult intensive care unit associated with pain as self-reported at the end of the intensive care unit stay.

BACKGROUND: The short-term and long-term consequences of the most frequent painful procedures performed in the ICU are unclear. This study aimed to identify the risk factors associated with pain-related discomfort perceived by critically ill patients during the whole ICU stay as self-reported by patients at the end of their ICU stay. METHODS: The study involved 34 ICUs. Adult patients who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Discomforts, including the pain-related discomfort, were assessed using the French 18-item questionnaire on discomfort in ICU patients, the "Inconforts des Patients de REAnimation" (IPREA). Patients scored each item from 0 (minimal discomfort) to 10 (maximal discomfort). Associations between patient characteristics at ICU admission, life support therapies and main potentially painful procedures performed during the ICU stay and pain-related discomfort scores assessed at the end of the ICU stay were analyzed. RESULTS: Patients with complete IPREA questionnaires (n = 2130) were included. The median pain-related discomfort score was 3 (IQR 0-5). From the univariate analysis, pain-related discomfort scores were negatively correlated with age and positively correlated with ICU stay duration; surgical patients reported significant higher pain-related discomfort scores than medical patients; chest drain insertion, chest drain removal, use of bladder catheter, central venous catheter (CVC) insertion, complex dressing change, and intra-hospital transport were associated with pain-related discomfort scores. From the multivariate analyses using generalized estimating equations models, only age, chest drain removal, use of a bladder catheter, CVC insertion, and intra-hospital transport were the main risk factors associated with pain-related discomfort scores. CONCLUSION: Patients who underwent chest drain removal, bladder catheter, CVC insertion, and intra-hospital transport during their ICU stay reported higher pain-related discomfort scores (with respect to the whole ICU stay and assessed at the end of their ICU stay) than patients who did not experience these events. This study may pave the way for further targeted studies aiming at investigating a causal link between these common procedures in the ICU and adult critically ill patients' perceptions of their ICU stay regarding recalled pain. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934, retrospectively registered on May 13, 2015.

Tailored multicomponent program for discomfort reduction in critically ill patients may decrease post-traumatic stress disorder in general ICU survivors at 1 year.

PURPOSE: Reducing discomfort in the intensive care unit (ICU) should have a positive effect on long-term outcomes. This study assessed whether a tailored multicomponent program for discomfort reduction was effective in reducing post-traumatic stress disorder (PTSD) symptoms at 1 year in general ICU survivors. METHODS: This study is a prospective observational comparative effectiveness cohort study involving 30 ICUs. It was an extension of the IPREA3 study, a cluster-randomized controlled trial designed to assess the efficacy of a tailored multicomponent program to reduce discomfort in critically ill patients. The program included assessment of ICU-related self-perceived discomforts, immediate and monthly feedback to the healthcare team, and site-specific tailored interventions. The exposure was the implementation of this program. The eligible patients were exposed versus unexposed general adult ICU survivors. The prevalence of substantial PTSD symptoms at 1 year was assessed based on the Impact of Event Scale-Revised (IES-R). RESULTS: Of the 1537 ICU survivors included in the study, 475 unexposed patients and 344 exposed patients had follow-up data at 1 year: 57 (12.0%) and 21 (6.1%) presented with PTSD at 1 year, respectively (p = 0.004). Considering the clustering and after adjusting for age, gender, McCabe classification, and ICU-related self-perceived overall discomfort score, exposed patients were significantly less likely than unexposed patients to have substantial PTSD symptoms at 1 year (p = 0.015). CONCLUSIONS: Implementation of a tailored multicomponent program in the ICU that has proved to be effective for reducing self-perceived discomfort in general adult ICU survivors also reduced the prevalence of substantial PTSD symptoms at 1 year. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02762409.

Assessment of patients' self-perceived intensive care unit discomforts: Validation of the 18-item version of the IPREA.

BACKGROUND AND AIMS: We reported the validation of the 18-item version of the 'Inconforts des Patients de REAnimation (IPREA)' questionnaire that includes 2 new items exploring feeling depressed and shortness of breath during an intensive care unit (ICU) stay. METHODS: The validation process was integrated in a multicenter, cluster-randomized, controlled, two-parallel group study built to assess the effectiveness of a tailored multicomponent program for reducing self-perceived discomfort in the ICU. All patients aged 18 years or older who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Data collection included demographics (sex, age), type of admission (medical and surgical), health status scores at admission (Knaus score and McCabe index, Simplified Acute Physiology Score (SAPS) II), specific ICU therapeutics such as mechanical ventilation (MV), noninvasive ventilation (NIV), use of vasopressors, or renal replacement therapy (RRT), and ICU stay duration. RESULTS: A total of 994 patients were included. The initial structure of IPREA was confirmed using confirmatory factor analysis showing satisfactory fit (RMSEA at 0.042, CFI at 0.912). No multidimensional structure was identified, allowing the calculation of an overall discomfort score. The three highest discomforts were sleep deprivation, thirst, and perfusion lines and other devices, and the 3 lowest discomforts were limited visiting hours, hunger, and isolation. The overall discomfort score of the 18-item version of IPREA did not differ between men and women. Higher age was significantly correlated with a lower overall discomfort score. While MV was not linked to self-reported discomfort, patients treated by NIV reported higher overall discomfort scores than patients not treated by NIV. CONCLUSION: The 18-item version of IPREA is easy to use and possesses satisfactory psychometric properties. The availability of a reliable and valid French questionnaire asking about patients' self-perceived ICU discomforts enables feedback from the health care team to be incorporated in a continuous quality health care improvement strategy. TRIAL REGISTRATION: clinicaltrial.gov NCT02442934 (registration date: May 18, 2015, retrospectively registered).

A tailored multicomponent program to reduce discomfort in critically ill patients: a cluster-randomized controlled trial.

PURPOSE: Critically ill patients are exposed to stressful conditions and experience several discomforts. The primary objective was to assess whether a tailored multicomponent program is effective for reducing self-perceived discomfort. METHODS: In a cluster-randomized two-arm parallel trial, 34 French adult intensive care units (ICUs) without planned interventions to reduce discomfort were randomized, 17 to the arm including a 6-month period of program implementation followed by a 6-month period without the program (experimental group), and 17 to the arm with an inversed sequence (control group). The tailored multicomponent program consisted of assessment of ICU-related self-perceived discomforts, immediate and monthly feedback to healthcare teams, and site-specific tailored interventions. The primary outcome was the overall discomfort score derived from the 16-item IPREA questionnaire (0, minimal, 100, maximal overall discomfort) and the secondary outcomes were the discomfort scores of each IPREA item. IPREA was administered on the day of ICU discharge with a considered timeframe from the ICU admission until ICU discharge. RESULTS: During a 1-month assessment period, 398 and 360 patients were included in the experimental group and the control group, respectively. The difference (experimental minus control) of the overall discomfort score between groups was - 7.00 (95% CI - 9.89 to - 4.11, p < 0.001). After adjustment (age, gender, ICU duration, mechanical ventilation duration, and type of admission), the program effect was still positive for the overall discomfort score (difference - 6.35, SE 1.23, p < 0.001) and for 12 out of 16 items. CONCLUSIONS: This tailored multicomponent program decreased self-perceived discomfort in adult critically ill patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934.

Use of near-infrared spectroscopy in predicting response to intravenous fluid load in anaesthetized infants.

INTRODUCTION: The prediction of fluid responsiveness in paediatrics and infants remains problematic. We sought to test the validity of the measurement of StcO2 as a predictive parameter of fluid responsiveness in infants less than one year old during non-cardiac surgery. MATERIALS AND METHODS: This was a prospective observational study on infants aged less than 1 year without any cardiac disease during the intraoperative period of non-cardiac surgery. Cerebral oxygen saturation (StcO2) was obtained using infrared spectroscopic INVOS® monitors. Reference values were obtained 10 minutes after intubation. Fluid load indications were dependent on the anaesthesiologist caring for the patient. The objective of this study was to determine the accuracy of StcO2 values before vascular filling (StcO2B) and the difference in StcO2 values between the reference value and before vascular filling (ΔStcO2), in predicting vascular filling response defined as an increase in mean arterial pressure over 15%. Statistical analysis was carried out using ROC curve analysis with determination of grey zones. RESULTS: Twenty-nine patients were eligible for this study, 23 were included in the study (one intravenous fluid challenge per patient). There were 10 responders and 13 non-responders. The StcO2B and the ΔStcO2 were significantly different between responders and non-responders. Analysis of the ROC curve found an area under the curve of 0.75 [95% CI 0.56 to 0.95] for StcO2B and 0.83 [95% CI 0.66 to 0.99] for ΔStcO2. The grey-areas were [59-78] and [16-28] for StcO2B and ΔStcO2. CONCLUSION: NIRS appears to be an interesting additional tool for predicting an increase of blood pressure in response to intraoperative fluid challenge in infants less than one year old.

Treatment of Highly Virulent Extraintestinal Pathogenic Escherichia coli Pneumonia With Bacteriophages.

OBJECTIVE: To study the effect of bacteriophage treatment on highly virulent extraintestinal Escherichia coli pneumonia in mice and compare it with conventional antimicrobial treatment. DESIGN: Animal investigation. SETTING: University research laboratory. SUBJECTS: Pathogen-free 8-week-old Balb/cJRj male mice. INTERVENTIONS: Two bacteriophages (536_P1 and 536_P7) were isolated from sewage using strain 536, a highly virulent extraintestinal E. coli. Their in vitro and in vivo efficacy against strain 536 and a ventilator-associated pneumonia E. coli were tested. The first group of mice were infected by intranasal instillation of bioluminescent strain 536 and received 536_P1 intranasally, ceftriaxone, or control. The second group of mice was infected with the ventilator-associated pneumonia strain and received 536_P7. Adaptation of 536_P7 to this clinical isolate was also evaluated in vitro and in vivo. MEASUREMENTS AND MAIN RESULTS: In vivo efficacy of bacteriophage and antibiotic treatment were assessed by recording bioluminescence for short-time periods and by recording body weight and survival of mice for longer periods. Both treatments improved survival compared with control (100% vs 0%), and in vivo bioluminescence recordings showed a similar rapid decrease of emitted light, suggesting prompt bacterial clearance. The majority of mice infected by the ventilator-associated pneumonia strain were not rescued by treatment with 536_P7; however, in vitro adaptation of this bacteriophage toward the ventilator-associated pneumonia strain led to isolate a variant which significantly improved in vivo treatment efficacy (animal survival increased from 20% to 75%). CONCLUSIONS: Bacteriophage treatment was as effective as antibiotherapy to provide 100% survival rate in a lethal model of highly virulent E. coli pneumonia. Adaptation of a bacteriophage is a rapid solution to improve its efficacy toward specific strains. These results suggest that phage therapy could be a promising therapeutic strategy for ventilator-associated pneumonia.