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1.  Multiplex PCR performed of bronchoalveolar lavage fluid increases pathogen identification rate in critically ill patients with pneumonia: a pilot study 
Background
In critically ill patients with pneumonia, accurate microorganism identification allows appropriate antibiotic treatment. In patients undergoing bronchoalveolar lavage (BAL), direct examination of the fluid using Gram staining provides prompt information but pathogen identification accuracy is low. Culture of BAL fluid is actually the reference, but it is not available before 24 to 48 h. In addition, pathogen identification rate observed with direct examination and culture is decreased when antibiotic therapy has been given prior to sampling. We therefore assessed, in critically ill patients with suspected pneumonia, the performance of a multiplex PCR (MPCR) to identify pathogens in BAL fluid. This study is a prospective pilot observation.
Methods
We used a MPCR detecting 20 types of microorganisms. Direct examination, culture, and MPCR were performed on BAL fluid of critically ill patients with pneumonia suspicion. The final diagnosis of infective pneumonia was retained after the medical chart was reviewed by two experts. Pathogen identification rate of direct examination, culture, and MPCR in patients with confirmed pneumonia was compared.
Results
Among the 65 patients with pneumonia suspicion, the diagnosis of pneumonia was finally retained in 53 cases. Twenty nine (55%) were community-acquired pneumonia and 24 (45%) were hospital acquired. Pathogen identification rate with MPCR (66%) was greater than with culture (40%) and direct examination (23%) (p =0.01 and p <0.001, respectively). When considering only the microorganisms included in the MPCR panel, the pathogen identification rate provided by MPCR reached 82% and was still higher than with culture (35%, p <0.001) and direct examination (21%, p <0.001). Pathogen identification rate provided by MPCR was not modified in the case of previous antibiotic treatment (66% vs. 64%, NS) and was still better than with culture (23%, p <0.001).
Conclusions
The results of this pilot study suggest that in critically ill patients, MPCR performed on BAL fluid could provide higher identification rate of pathogens involved in pneumonia than direct examination and culture, especially in patients having received antimicrobial treatment.
doi:10.1186/s13613-014-0035-7
PMCID: PMC4273674  PMID: 25593751
Multiplex PCR; SeptiFast®; Bronchoalveolar lavage; Antibiotic therapy; Prior antibiotic treatment; Community-acquired pneumonia; Hospital-acquired pneumonia; Ventilator-acquired pneumonia
2.  Alteration of skin perfusion in mottling area during septic shock 
Background
Mottling score has been reported to be a strong predictive factor during septic shock. However, the pathophysiology of mottling remains unclear.
Methods
In patients admitted in ICU for septic shock, we measured on the same area the mean skin perfusion by laser Doppler, the mottling score, and variations of both indices between T1 (6 hours after vasopressors were started) and T2 (24 hours later).
Results
Fourteen patients were included, SAPS II was 56 [37–71] and SOFA score at T1 was 10 [7–12]. The mean skin surface area analyzed was 4108 ± 740 mm2; 1184 ± 141 measurements were performed over each defined skin surface area. Skin perfusion was significantly different according to mottling score and decreased from 37 [31–42] perfusion units (PUs) for a mottling score of [0–1] to 22 [20–32] PUs for a mottling score of [2–3] and 23 [16–28] for a score of [4–5] (Kruskal-Wallis test, P = 0.05). We analyzed skin perfusion changes during resuscitation in each patient and together with mottling score variations between T1 and T2 using a Wilcoxon signed-rank test. Among the 14 patients included, mottling score increased (worsened) in 5 patients, decreased (improved) in 5 patients, and remained stable in 4 patients. Baseline skin perfusion at T1 was arbitrarily scored 100%. Mean skin perfusion significantly decreased in all the patients whose mottling score worsened from 100% baseline to 63.2 ± 10.7% (P = 0.001), mean skin perfusion significantly increased in all patients whose mottling score improved from 100% baseline to 172.6 ± 46.8% (P = 0.001), and remained stable in patients whose mottling score did not change (100.5 ± 6.8%, P = 0.95).
Conclusions
We have shown that mottling score variations and skin perfusion changes during septic shock resuscitation were correlated, providing additional evidence that mottling reflects skin hypoperfusion.
doi:10.1186/2110-5820-3-31
PMCID: PMC3848827  PMID: 24040941
Septic shock; Microcirculation; Mottling; Intensive care medicine
3.  Endotoxemia and mortality prediction in ICU and other settings: underlying risk and co-detection of gram negative bacteremia are confounders 
Critical Care  2012;16(4):R148.
Introduction
The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship.
Methods
Published studies with ≥10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots.
Results
Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR <2) or non-significantly increased for groups two (GN bacteremia alone) and three (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co-detected) each versus patient group four (neither endotoxemia nor GN bacteremia detected). The ORs were markedly higher for group one versus group four (OR 6.9; 95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among groups one versus two are significantly unequal.
Conclusions
The co-detection of GN bacteremia and endotoxemia is predictive of increased mortality risk versus the detection of neither but only in studies undertaken in a non-ICU setting. Variation in GN bacteremia species types and underlying risk are likely unrecognized confounders in the individual studies.
doi:10.1186/cc11462
PMCID: PMC3580737  PMID: 22871090
4.  Comparison of superior vena cava and femoroiliac vein pressure according to intra-abdominal pressure 
Background
Previous studies have shown a good agreement between central venous pressure (CVP) measurements from catheters placed in superior vena cava and catheters placed in the abdominal cava/common iliac vein. However, the influence of intra-abdominal pressure on such measurements remains unknown.
Methods
We conducted a prospective, observational study in a tertiary teaching hospital. We enrolled patients who had indwelling catheters in both superior vena cava (double lumen catheter) and femoroiliac veins (dialysis catheter) and into the bladder. Pressures were measured from all the sites, CVP, femoroiliac venous pressure (FIVP), and intra-abdominal pressure.
Results
A total of 30 patients were enrolled (age 62 ± 14 years; SAPS II 62 (52–76)). Fifty complete sets of measurements were performed. All of the studied patients were mechanically ventilated (PEP 3 cmH20 (2–5)). We observed that the concordance between CVP and FIVP decreased when intra-abdominal pressure increased. We identified 14 mmHg as the best intra-abdominal pressure cutoff, and we found that CVP and FIVP were significantly more in agreement below this threshold than above (94% versus 50%, P = 0.002).
Conclusions
We reported that intra-abdominal pressure affected agreement between CVP measurements from catheter placed in superior vena cava and catheters placed in the femoroiliac vein. Agreement was excellent when intra-abdominal pressure was below 14 mmHg.
doi:10.1186/2110-5820-2-21
PMCID: PMC3424143  PMID: 22742667
Intensive unit care; Central venous pressure; Superior vena cava; Femoroiliac vena; Intra-abdominal pressure
5.  Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study 
Background
We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device.
Methods
We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin].
Results
Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71–48.8; p < 0.001).
Conclusions
The administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.
doi:10.1186/2110-5820-2-16
PMCID: PMC3409028  PMID: 22697362
Hypoglycemia; Intensive care unit; Infusion tubing; Central venous catheter; Intensive insulin therapy
6.  Emerging Severe and Fatal Infections Due to Klebsiella pneumoniae in Two University Hospitals in France▿ 
Journal of Clinical Microbiology  2011;49(8):3012-3014.
Severe infections caused by hypermucoviscous Klebsiella pneumoniae have been reported in Southeast Asian countries over the past several decades. This report shows their emergence in France, with 12 cases observed during a 2-year period in two university hospitals. Two clones (sequence type 86 [ST86] and ST380) of serotype K2 caused five rapidly fatal bacteremia cases, three of which were associated with pneumonia, whereas seven liver abscess cases were caused by K1 strains of ST23.
doi:10.1128/JCM.00676-11
PMCID: PMC3147753  PMID: 21677064
7.  TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II–infused mice 
Complicated abdominal aortic aneurysm (AAA) is a major cause of mortality in elderly men. Ang II–dependent TGF-β activity promotes aortic aneurysm progression in experimental Marfan syndrome. However, the role of TGF-β in experimental models of AAA has not been comprehensively assessed. Here, we show that systemic neutralization of TGF-β activity breaks the resistance of normocholesterolemic C57BL/6 mice to Ang II–induced AAA formation and markedly increases their susceptibility to the disease. These aneurysms displayed a large spectrum of complications on echography, including fissuration, double channel formation, and rupture, leading to death from aneurysm complications. The disease was refractory to inhibition of IFN-γ, IL-4, IL-6, or TNF-α signaling. Genetic deletion of T and B cells or inhibition of the CX3CR1 pathway resulted in partial protection. Interestingly, neutralization of TGF-β activity enhanced monocyte invasiveness, and monocyte depletion markedly inhibited aneurysm progression and complications. Finally, TGF-β neutralization increased MMP-12 activity, and MMP-12 deficiency prevented aneurysm rupture. These results clearly identify a critical role for TGF-β in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome.
doi:10.1172/JCI38136
PMCID: PMC2810071  PMID: 20101093
8.  Does nonadherence to local recommendations for empirical antibiotic therapy on admission to the intensive care unit have an impact on in-hospital mortality? 
Objective
1/ To evaluate if empirical antibiotic prescription on admission to our intensive care unit (ICU) respects the local recommendations for antibiotic prescription and to identify predictors of nonadherence to these guidelines. 2/ To assess whether nonadherence to the guidelines is associated with increased in-hospital mortality due to the initial infection.
Materials and methods
This was a prospective six-month observational study performed in a 14-bed medical ICU. Patients were included if they received curative antibiotic therapy on admission. Respect of the local treatment recommendations was evaluated according to adherence to the local empirical guidelines defined in a 80-page booklet which is given in our hospital to every physician.
Results
Among 132 antibiotic prescriptions, 21 (16%) were unjustified (absence of infection), 17 (13%) were microbiologically documented at admission, and nine (7%) were given for infections from unknown origin. Among the 85 (64%) empirical prescriptions that could be evaluated for adherence to local recommendations, nine (11%) were inappropriate and 76 (89%) appropriate. In univariate analysis hospital-acquired infection was the sole predictor of inappropriate treatment (p = 0.0475). Independent predictors of in-hospital mortality due to the initial infection were inappropriate empirical treatment (odds ratio [OR] = 14.64, 95% confidence interval [CI]: 2.17–98.97; p = 0.006), prescription of fluoroquinolones (OR = 8.22, 95% CI: 1.88–35.95; p = 0.005) and a higher Simplified Acute Physiology Score II score (per one-point increment (OR = 1.04, 95% CI: 1.01–1.07; p = 0.02).
Conclusion
Nonadherence to local empirical antibiotic therapy guidelines was associated with increased in-hospital mortality due to the initial infection.
PMCID: PMC2710381  PMID: 19707259
antimicrobial therapy; appropriateness; mortality; intensive care unit
9.  A thyrotoxicosis outbreak due to dietary pills in Paris 
Three women were consecutively admitted to our medical intensive care unit for thyrotoxicosis after the ingestion of dietary pills accidentally containing high levels of thyroxin. These cases were observed during an outbreak in the Paris area. Despite similar blood levels of thyroid hormones, their clinical presentation and outcome were very different. One patient developed febrile confusion and died from malignant hyperthermia. The second one had progressive confusion requiring mechanical plasma exchange therapy and had a favorable outcome. The third one had very moderate symptoms. These exceptional observations raise several issues concerning diagnosis, physiopathology and treatment of thyrotoxicosis factitia.
PMCID: PMC2643119  PMID: 19337445
thyrotoxicosis; dietary pills; thyroxin

Results 1-9 (9)