Colonization resistance against multi-drug-resistant bacteria: a narrative review.

Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated.

High incidence of postoperative infections after pancreaticoduodenectomy: A need for perioperative anti-infectious strategies.

OBJECTIVES: Postoperative infections occur frequently after pancreaticoduodenectomy, especially in patients with bile colonization. Recommendations for perioperative anti-infectious treatment are lacking, and clinical practice is heterogenous. We have analyzed the effects of bile colonization and antibiotic prophylaxis on postoperative infection rates, types and therapeutic consequences. METHODS: Retrospective observational study in patients undergoing pancreaticoduodenectomy with intraoperative bile culture. Data on postoperative infections and non-infectious complications, bile cultures and antibiotic prophylaxis adequacy to biliary bacteria were collected. RESULTS: Among 129 patients, 53% had a positive bile culture and 23% had received appropriate antibiotic prophylaxis. Postoperative documented infection rate was over 40% in patients with or without bile colonization, but antibiotic therapy was more frequent in positive bile culture patients (77% vs. 57%, P=0,008). The median duration of antibiotic therapy was 11 days and included a broad-spectrum molecule in 42% of cases. Two-thirds of documented postoperative infections involved one or more bacteria isolated in bile cultures, which was associated with a higher complication rate. While bile culture yielded Gram-negative bacilli (57%) and Gram-positive cocci (43%), fungal microorganisms were scarce. Adequate preoperative antibiotic prophylaxis according to bile culture was not associated with reduced infectious or non-infectious complication rates. CONCLUSION: Patients undergoing pancreaticoduodenectomy experience a high rate of postoperative infections, often involving bacteria from perioperative bile culture when positive, with no preventive effect of an adequate preoperative antibiotic prophylaxis. Increased postoperative complications in patients with bile colonization may render necessary a perioperative antibiotic treatment targeting bile microorganisms. Further prospective studies are needed to improve the anti-infectious strategy in these patients.

Spontaneous decolonization during hospitalization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales.

This study aimed to analyse the frequency of occurrence of spontaneous decolonization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in order to assess the added value of continuing weekly ESBL-E rectal carriage screening in these patients. In total, 49,468 weekly rectal screening samples taken from 20,846 patients over 12 years were included. Among the 4280 ESBL-E carriers, only 109 patients (2.5%) could be considered decolonized at the end of their hospitalization with at least three consecutive negative samples. Overall, 7957 samples (16.1%) were requested for patients already identified as ESBL-E carriers. Avoiding unnecessary weekly screening following positive ESBL-E colonization results could decrease nursing and laboratory work loads.

Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: The READIAB study.

OBJECTIVE: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. METHODS: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. MAIN RESULTS: The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P=0.078): OR(peroneTcopy): 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P=0.026), but was no longer significant at 1 year (P=0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P<0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32-2.28; P<0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P=0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P=0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P=0.72) or 1 year (P=0.64). CONCLUSION: This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.

Influence of bacterial resistance on mortality in intensive care units: a registry study from 2000 to 2013 (IICU Study).

BACKGROUND: Bacterial resistance to antibiotics is a daily concern in intensive care units. However, few data are available concerning the clinical consequences of in-vitro-defined resistance. AIM: To compare the mortality of patients with nosocomial infections according to bacterial resistance profiles. METHODS: The prospective surveillance registry in 29 French intensive care units (ICUs) participating during the years 2000-2013 was retrospectively analysed. All patients presenting with a nosocomial infection in ICU were included. FINDINGS: The registry contained 88,000 eligible patients, including 10,001 patients with a nosocomial infection. Among them, 3092 (36.7%) were related to resistant micro-organisms. Gram-negative bacilli exhibited the highest rate of resistance compared to Gram-positive cocci (52.8% vs 48.1%; P < 0.001). In-hospital mortality was higher in cases of patients with antibiotic-resistant infectious agents (51.9% vs 45.5%; P < 0.001), and critical care length of stay was longer (33 ± 26 vs 29 ± 22 days; P < 0.001). These results remained significant after SAPS II matching (P < 0.001) and in the Gram-negative bacilli and Gram-positive cocci subgroups. No difference in mortality was found with respect to origin prior to admission. CONCLUSION: Patients with bacterial resistance had higher ICU mortality and increased length of stay, regardless of the bacterial species or origin of the patient.

French lyophilized plasma versus fresh frozen plasma for the initial management of trauma-induced coagulopathy: a randomized open-label trial.

Essentials An immediate supply of plasma in case of trauma-induced coagulopathy is required. The Traucc trial compared French Lyophilised Plasma (FLyP) and Fresh Frozen Plasma (FFP). FLyP achieved higher fibrinogen concentrations compared with FFP. FLyP led to a more rapid coagulopathy improvement than FFP. SUMMARY: Background Guidelines recommend beginning hemostatic resuscitation immediately in trauma patients. We aimed to investigate if French lyophilized plasma (FLyP) was more effective than fresh frozen plasma (FFP) for the initial management of trauma-induced coagulopathy. Methods In an open-label, phase 3, randomized trial (NCT02750150), we enrolled adult trauma patients requiring an emergency pack of 4 plasma units within 6 h of injury. We randomly assigned patients to receive 4-FLyP units or 4-FFP units. The primary endpoint was fibrinogen concentration at 45 min after randomization. Secondary outcomes included time to transfusion, changes in hemostatic parameters at different time-points, blood product requirements and 30-day in-hospital mortality. Results Forty-eight patients were randomized (FLyP, n = 24; FFP, n = 24). FLyP reduced the time from randomization to transfusion of first plasma unit compared with FFP (median[IQR],14[5-30] vs. 77[64-90] min). FLyP achieved a higher fibrinogen concentration 45 min after randomization compared with FFP (baseline-adjusted mean difference, 0.29 g L-1 ; 95% confidence interval [CI], 0.08-0.49) and a greater improvement in prothrombin time ratio, factor V and factor II. The between-group differences in coagulation parameters remained significant at 6 h. FLyP reduced fibrinogen concentrate requirements. Thirty-day in-hospital mortality rate was 22% with FLyP and 29% with FFP. Conclusion FLyP led to a more rapid, pronounced and extended increase in fibrinogen concentrations and coagulopathy improvement compared with FFP in the initial management of trauma patients. FLyP represents an attractive option for trauma management, especially when facing logistical issues such as combat casualties or mass casualties related to terror attacks or disasters.

Biphasic lung injury during Streptococcus pneumoniae infection in a murine model.

OBJECTIVES: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. We aimed to analyze the epithelial response to S. pneumoniae-induced lung injury. METHODS: Using an in vitro model with 16HBE cells and experimental in vivo murine model of acute lung injury, we analyzed the epithelial response to S. pneumoniae. Lung epithelial cell monolayers were exposed to S. pneumoniae and permeability was assessed by transepithelial resistance (TER) measurement and organization and expression of junction proteins. Functional consequences were studied with an in vivo murine model measuring alveolar permeability, distal alveolar fluid clearance (DAFC), and the alveolar inflammatory response. RESULTS: In vitro, S. pneumoniae induced a dose-dependent decrease in transepithelial resistance, which was associated with significant modifications in the organization of junction proteins assessed by immunofluorescence staining and expression after 6hours of exposure. In vivo, S. pneumoniae induced a transient increase in alveolar permeability with an adequate increase in DAFC 6hours post infection. In a second phase, a permanent increased permeability was associated with a major decrease in DAFC. CONCLUSION: Overall, the epithelial response to S. pneumoniae followed a biphasic pattern with an initial reversible increase in permeability related to the alteration of tight and adherens junctions and a second phase associated with an epithelial injury with a major increase in permeability with a decreased DAFC reflecting an injured alveolar capillary barrier.

Compliance with evidence-based clinical management guidelines in bleeding trauma patients.

BACKGROUND: In 2007, the multidisciplinary European Task Force for Advanced Bleeding Care in Trauma published guidelines for the management of the bleeding trauma patient. The present study aimed to assess compliance with the European guidelines during the first 24 h in a level I trauma centre and to determine whether compliance impacts mortality. METHODS: This was a retrospective study of consecutive bleeding trauma patients referred to a university hospital in France between 2010 and 2014. A reference document was developed on the basis of the European guidelines to transform the guidelines pragmatically into 22 objectively measurable criteria. We measured per-patient and per-criterion compliance rates and assessed the impact of guideline compliance on mortality. RESULTS: A total of 121 bleeding trauma patients were included. The median (interquartile range) per-patient compliance rate was 75 (65-82)% and the per-criterion compliance rate 64 (57-81)%. Mortality rates were 18 and 32% at 24 h and 30 days, respectively. After adjusting for injury severity, per-patient compliance rates were associated with decreased mortality at 24 h (odds ratio per 10% increase in patient compliance score, 0.43; 95% confidence interval 0.26-0.71; P = 0.0001) and at 30 days (odds ratio per 10% increase in patient compliance score, 0.47; 95% confidence interval 0.31-0.72; P = 0.0004). CONCLUSIONS: We found that compliance with protocols based on European guidelines impacts trauma outcome, because patient compliance was associated with survival. Further work is needed to improve adherence to these guidelines, with ongoing monitoring to ensure best practice and optimal patient outcome.

The Dose Response Multicentre Investigation on Fluid Assessment (DoReMIFA) in critically ill patients.

BACKGROUND: The previously published "Dose Response Multicentre International Collaborative Initiative (DoReMi)" study concluded that the high mortality of critically ill patients with acute kidney injury (AKI) was unlikely to be related to an inadequate dose of renal replacement therapy (RRT) and other factors were contributing. This follow-up study aimed to investigate the impact of daily fluid balance and fluid accumulation on mortality of critically ill patients without AKI (N-AKI), with AKI (AKI) and with AKI on RRT (AKI-RRT) receiving an adequate dose of RRT. METHODS: We prospectively enrolled all consecutive patients admitted to 21 intensive care units (ICUs) from nine countries and collected baseline characteristics, comorbidities, severity of illness, presence of sepsis, daily physiologic parameters and fluid intake-output, AKI stage, need for RRT and survival status. Daily fluid balance was computed and fluid overload (FO) was defined as percentage of admission body weight (BW). Maximum fluid overload (MFO) was the peak value of FO. RESULTS: We analysed 1734 patients. A total of 991 (57 %) had N-AKI, 560 (32 %) had AKI but did not have RRT and 183 (11 %) had AKI-RRT. ICU mortality was 22.3 % in AKI patients and 5.6 % in those without AKI (p < 0.0001). Progressive fluid accumulation was seen in all three groups. Maximum fluid accumulation occurred on day 2 in N-AKI patients (2.8 % of BW), on day 3 in AKI patients not receiving RRT (4.3 % of BW) and on day 5 in AKI-RRT patients (7.9 % of BW). The main findings were: (1) the odds ratio (OR) for hospital mortality increased by 1.075 (95 % confidence interval 1.055-1.095) with every 1 % increase of MFO. When adjusting for severity of illness and AKI status, the OR changed to 1.044. This phenomenon was a continuum and independent of thresholds as previously reported. (2) Multivariate analysis confirmed that the speed of fluid accumulation was independently associated with ICU mortality. (3) Fluid accumulation increased significantly in the 3-day period prior to the diagnosis of AKI and peaked 3 days later. CONCLUSIONS: In critically ill patients, the severity and speed of fluid accumulation are independent risk factors for ICU mortality. Fluid balance abnormality precedes and follows the diagnosis of AKI.

Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial.

BACKGROUND: Beneficial effects of tranexamic acid (TA) have been established in surgery and trauma. In ongoing postpartum haemorrhage (PPH), a moderate reduction of blood loss was observed in a previously published randomized controlled trial. Analysis of haemostasis parameters obtained from samples collected as part of this study are presented. METHODS: Women with PPH >800 ml after vaginal delivery were assigned to receive either TA (4 g over 1 h, then 1 g per h over six h) (TA) or not (H). A non-haemorrhagic group (NH), <800 ml blood loss, was included as postpartum reference. At four time-points (enrolment, +30 min, +2 h, +6 h), haemostasis was assessed. Haemostasis assays were performed blinded to group allocation. Data were expressed as median [interquartiles] and compared with non-parametric tests. RESULTS: In H compared with NH group, D-dimers increase (3730 ng ml(-1) [2468-8493] vs 2649 [2667-4375]; P=0.0001) and fibrinogen and factor II decrease were observed at enrolment and became maximal 2 h later. When comparing TA to H patients, the increase in Plasmin-Antiplasmin-complexes at +30 min (486 ng ml(-1) [340-1116] vs 674 [548-1640]; P=0.03) and D-dimers at +2 h (3888 ng ml(-1) [2688-6172] vs 7495 [4400-15772]; P=0.0001) was blunted. TA had no effect on fibrinogen decrease. CONCLUSIONS: This study provides biological evidence of an early increase in D-dimers and plasmin-antiplasmin complexes associated with active post-partum haemorrhage and its attenuation by the early use of a clinically effective high dose of TA, opening the perspective of dose ranging studies to determinate the optimal dose and timing in this setting. CLINICAL TRIAL REGISTRATION: ISRCTN09968140.

Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus involved in severe acute respiratory distress syndrome (ARDS) and rapid renal failure. Hospital outbreak and nosocomial transmission were reported, however, several issues remain on the viral excretion course. OBJECTIVES: Describe the kinetics and pattern of viral excretion in two infected patients. STUDY DESIGN: After the initial diagnosis, blood, urine, rectal and respiratory samples were collected regularly, aliquoted and stored at -80°C. Real-time reverse transcriptase polymerase chain reaction assay targeted the UpE and Orf1a regions of the MERS-CoV genome. RESULTS: In patient 1, who died of refractory ARDS and renal failure, MERS-CoV RNA was detected in pharyngeal and tracheal swabs, as well blood samples and urine samples until the 30th day. Rectal swabs were negative. Patient 2 also developed multiple-organ failure, but survived, with persisting renal insufficiency (creatinine clearance at 30 mL/min) and persistent interstitial syndrome albeit weaned off mechanical ventilation and no longer requiring oxygen. Tracheal aspirations were positive until the 33rd day, while nasopharyngeal swabs were negative. All other biological samples were negative. DISCUSSION: Lower respiratory tract excretion of MERS-CoV could be observed for more than one month. The most severely ill patient presented an expression of the virus in blood and urine, consistent with a type-1 interferon mediated immunological response impaired in patient 1, but developed by patient 2. These results suggest that infection control precautions must be adequately evaluated in clinical wards and laboratories exposed to MERS-CoV.

Candida albicans and Pseudomonas aeruginosa interactions: more than an opportunistic criminal association?

Pseudomonas aeruginosa and Candida albicans are frequently coexisting opportunistic pathogens, responsible for colonization and infection in predisposed patients. They share a virulence specificity relying on auto-inducing, cell density-dependent molecules named quorum-sensing (QS). C. albicans virulence depends on its QS that influences morphological switch from yeast to filamentous form. Similarly, the production of P. aeruginosa virulence factors depends partly on QS molecules. Interactions have been investigated and demonstrated in vitro. P. aeruginosa may kill C. albicans either by producing toxins, such as pyocyanin, or by direct contact on its biofilm-dependent filamentous form. Cross-kingdom communication is a more subtle interaction: C. albicans can adapt its morphology in the presence of P. aeruginosa QS molecules, and inhibit P. aeruginosa QS-dependent virulence factor secretion, through farnesol, one of its QS molecule. But the in vivo relevance of these interactions is still controversial, as models of airway colonization/infection by C. albicans followed by subsequent P. aeruginosa pneumonia give contradictory results, suggesting the probable involvement of the immune system as a third party player. Finally, the authors of clinical studies performed in ventilated patients, indicate that C. albicans colonization could be a risk factor for P. aeruginosa pneumonia. The clinical outcome of C. albicans and P. aeruginosa interaction is uncertain, the virulence modulation demonstrated in these interactions opens new possibilities for future anti-infectious therapeutics.

Impact of a prophylactic strategy on the incidence of nausea and vomiting after general surgery.

BACKGROUND: This study aimed to evaluate the implementation of a strategy to prevent postoperative nausea and vomiting (PONV) in patients undergoing general surgery. STUDY DESIGN: Prospective observational study. METHODS: A first period was observational. During a second period, a strategy to prevent PONV was based on five risk factors (RF) identified after the first phase. From two RF, antiemetic treatment was given according to the number of RF. The incidence of PONV was recorded in postoperative anaesthesic care unit (PACU) and at the 24th postoperative hour (24h). RESULTS: We prospectively enrolled 823 patients. Implementation of a prophylactic PONV strategy was associated with a decrease of nausea in PACU from 29.9 to 9.8% (P<0.001) and at 24h from 19 to 10.3% (P<0.001). Vomiting decreased from 12.4 to 2.3% (P<0.001) in PACU and from 5.6 to 3.7% at 24h (non-significant). CONCLUSION: Prophylaxis of PONV by the administration of antiemetic treatment according to a strategy based on a local risk score was efficient and associated with a significant decrease of PONV.

Sevoflurane pre- and post-conditioning protect the brain via the mitochondrial K ATP channel.

BACKGROUND: This study aimed to evaluate whether exposure to sevoflurane at the onset of reperfusion provides protection similar to sevoflurane preconditioning and whether the effect depends on mitochondrial potassium ATP-dependent channel (mitoK(ATP)) in a rat model of focal cerebral ischaemia. METHODS: Adult Wistar male rats were subjected to focal cerebral ischaemia for 1 h followed by 24 h or 7 days of reperfusion. Preconditioning consisted of 15 min exposure to sevoflurane at 1 minimum alveolar concentration (2.6%) 72 h before ischaemia. Post-conditioning was performed by exposure to sevoflurane immediately at the onset of reperfusion or by a delayed exposure 5 min after the onset of reperfusion. The role of the mitoK(ATP) channel was assessed by i.p. injection of the selective blocker 5-hydroxydecanoate before each sevoflurane administration or by the mitoK(ATP) channel opener, diazoxide (DZX), given in place of sevoflurane. Cerebral infarct size, neurological deficit score, and motor coordination were evaluated 24 h and 7 days after reperfusion. RESULTS: Sevoflurane preconditioning and early post-conditioning reduced both cerebral infarct size and neurological defect score at 24 h of reperfusion whereas the sole sevoflurane post-conditioning improved motor coordination. At 7 days, only infarct volume remained lower in pre- and post-conditioned animals. Neuroprotection mediated by sevoflurane was lost when it was given 5 min after the onset of reperfusion and was abolished by inhibition of mitoK(ATP). DZX alone mimicked sevoflurane-induced pre- and post-conditioning. CONCLUSIONS: The pretreatment with sevoflurane or its early administration at reperfusion provides neuroprotection via mitoK(ATP) in a rat model of focal cerebral ischaemia.

Quorum-sensing activity and related virulence factor expression in clinically pathogenic isolates of Pseudomonas aeruginosa.

Respiratory isolates of Pseudomonas aeruginosa were collected from 58 critically-ill patients with ventilator-associated pneumonia. Expression of elastase and pyocyanin was assessed semi-quantitatively, while quorum-sensing activity was assessed by quantifying the levels of the autoinducers N-3-oxododecanoyl-L-homoserine lactone (C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL). Correlations were sought between quorum-sensing activity and the expression of these two virulence factors, and all results were compared to those obtained with the laboratory reference strains PA103, a strain defective in quorum-sensing, and PAO1, a functional quorum-sensing strain. More than two-thirds of clinically pathogenic isolates had increased levels of elastase and/or pyocyanin, and high quorum-sensing activity, as assessed by autoinducer levels. However, a strong correlation between quorum-sensing activity and virulence factor production was revealed only for elastase and not for pyocyanin (C12-HSL/elastase, r = 0.7, p 2 x 10(-9); C4-HSL/elastase, r = 0.7, p 2 x 10(-9)). These data suggest that the pathogenicity of P. aeruginosa isolates from critically-ill patients with ventilator-associated pneumonia is caused, at least in part, by an increase in elastase production regulated by quorum-sensing, while increased pyocyanin production in these isolates may be regulated predominantly by mechanisms other than quorum-sensing.

Non-invasive prediction of fluid responsiveness during major hepatic surgery.

BACKGROUND: The aim of this study was to evaluate potential predictors of fluid responsiveness obtained during major hepatic surgery. The predictors studied were invasive monitoring of intravascular pressures (radial and pulmonary artery catheter), including direct measurement of respiratory variation in arterial pulse pressure (PPVart), transoesophageal echocardiography (TOE), and non-invasive estimates of PPVart from the infrared photoplethysmography waveform from the Finapres (PPVfina) and the pulse oximetry waveform (PPVsat). METHODS: We conducted a prospective study of 54 fluid challenges (250 ml colloid) given for haemodynamic instability in eight patients undergoing hepatic resection. Fluid responsiveness was defined as an increase in stroke volume index (SVI) >or=10%. The following variables were recorded before each fluid challenge: right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), PPVart, PPVfina, PPVsat, and the TOE-derived variables left ventricular end-diastolic area index (LVEDAI), early/late (E/A) diastolic filling wave ratio, deceleration time of the E wave (MDT) of mitral flow and the systolic fraction of the pulmonary venous flow (SF). RESULTS: Only PPVfina, PPVart (both P<0.001), PPVsat (P=0.02), LVEDAI and MDT (both P=0.04) were different in responder vs non-responder fluid challenges. The areas under the receiver operating characteristic (ROC) curves were 0.81 (PPVfina), 0.79 (PPVart), 0.70 (LVEDAI), 0.68 (PPVsat and MDT), 0.63 (RAP), 0.62 (E/A), 0.55 (PAOP) and 0.42 (SF). The areas under the ROC curves for RAP, E/A, PAOP and SF were significantly less than that for PPVfina (P<0.05 in each case). Only PPVart (r=0.59, P=0.0001) and PPVfina (r=0.56, P=0.0001) correlated with the fluid challenge-induced changes in SVI. CONCLUSIONS: PPVart and PPVfina predict fluid responsiveness during major hepatic surgery. This suggests that intraoperative monitoring of fluid responsiveness may be implemented simply and non-invasively.

Targeting mechanisms of Pseudomonas aeruginosa pathogenesis.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for ventilator-acquired pneumonia, acute lower respiratory tract infections in immunocompromised patients and chronic respiratory infections in cystic fibrosis patients. High incidence, infection severity and increasing resistance characterize P. aeruginosa infections, highlighting the need for new therapeutic options. One such option is to target the many pathogenic mechanisms conferred to P. aeruginosa by its large genome encoding many different virulence factors. This article reviews the pathogenic mechanisms and potential therapies targeting these mechanisms in P. aeruginosa respiratory infections.