Comparison of albicans vs. non-albicans candidemia in French intensive care units

The AmarCand Study Group (ICU physicians): Drs. Allaouchiche (Lyon), Amigues (Montpellier), Ausseur (Saint Herblain), Azoulay (Paris), Badet (Lyon), Baldesi (Aix-en-Provence), Bastien (Bron), Baudin (Paris), Bayle (Lyon), Bazin (Clermont-Ferrand), Benayoun (Clichy), Blondeau (Roubaix), Bodin (Paris), Bollaert (Nancy), Bonadona (La Tronche), Bonnaire (Aulnay Sous Bois), Bonnivard (Montauban), Borne (Paris), Brabet (Montpellier), Branche (Lyon), Braud (Rouen), Bret (Lyon), Bretonnière (Nantes), Brocas (Evry), Brun (Bron), Bruneel (Versailles), Canevet (Armentières), Cantais (Toulon Armées), Carlet (Paris), Charbonneau (Caen), Charles (Dijon), Chastagner (Chamberry), Corne (Montpellier), Courte (Saint-Brieuc), Cousson (Reims), Cren (Morlaix), Diconne (Saint Etienne), Drouet (Saint-Denis), Dube (Angers), Duguet (Paris), Dulbecco (Antibes), Dumenil (Clamart), Dupont (Amiens), Durand (Grenoble), Durand-Gasselin (Toulon), Durocher (Lille), Fangio (Poissy), Fattouh (Mulhouse), Favier (Metz Armées), Fieux (Paris), Fleureau (Pessac), Freys (Strasbourg), Fulgencio (Paris), Gally (Mulhouse), Garnaud (Orléans), Garot (Tours), Gilhodes (Créteil), Girault (Rouen), Gouin (Marseille), Gouin (Rouen), Guidon (Marseille), Hérault (Grenoble), Hyvernat (Nice), Jobard (Monaco), Jospe (Saint Etienne), Kaidomar (Fréjus), Karoubi (Bobigny), Kherchache (Agen), Lacherade (Poissy), Lakermi (Paris), Lambiotte (Maubeuge), Lamia (Le Kremlin-Bicêtre), Lasocki (Paris), Launoy (Strasbourg), Le Guillou (Paris), Lefort (Saint-Denis), Lefrant (Nîmes), Lemaire (Roubaix), Lepape (Pierre-Bénite), Lepoutre (Lomme), Leroy (Lille), Leroy (Tourcoing), Loriferne (Bry-sur-Marne), Mahe (Nantes), Mandin (Gap), Marighy (Saint- Denis), Mathieu (Lille), Mathonnet (Paris), Megarbane (Paris), Mercat (Angers), Michel (Saint Herblain), Michelet (Marseille), Mimoz (Poitiers), Mohammedi (Lyon), Mouquet (Paris), Mourvillier (Paris), Navellou (Besançon), Novara (Paris), Obadia (Montreuil), Perrigault (Montpellier), Perrin (Marseille), Petit (Valence), Poussel (Metz), Rahmani (Strasbourg), Renard (La Roche sur Yon), Robert (Poitiers), Robert (Lyon), Saliba (Villejuif ), Sannini (Marseille), Santré (Annecy), Seguin (Rennes), Souweine (Clermont-Ferrand), Trouillet (Paris), Valentin (Besançon), Volatron (Rennes), Voltz (Vandoeuvre les Nancy), Winer (Saint Pierre), and Winnock (Bordeaux).International audienceINTRODUCTION: Candidemia raises numerous therapeutic issues for intensive care physicians. Epidemiological data that could guide the choice of initial therapy are still required. This analysis sought to compare the characteristics of intensive care unit (ICU) patients with candidemia due to non-albicans Candida species with those of ICU patients with candidemia due to Candida albicans. METHODS: A prospective, observational, multicenter, French study was conducted from October 2005 to May 2006. Patients exhibiting candidemia developed during ICU stay and exclusively due either to one or more non-albicans Candida species or to C. albicans were selected. The data collected included patient characteristics on ICU admission and at the onset of candidemia. RESULTS: Among the 136 patients analyzed, 78 (57.4%) had candidemia caused by C. albicans. These patients had earlier onset of infection (11.1 +/- 14.2 days after ICU admission vs. 17.4 +/- 17.7, p = 0.02), higher severity scores on ICU admission (SOFA: 10.4 +/- 4.7 vs. 8.6 +/- 4.6, p = 0.03; SAPS II: 57.4 +/- 22.8 vs. 48.7 +/- 15.5, P = 0.015), and were less often neutropenic (2.6% vs. 12%, p = 0.04) than patients with candidemia due to non-albicans Candida species. CONCLUSIONS: Although patients infected with Candida albicans differed from patients infected with non-albicans Candida species for a few characteristics, no clinical factor appeared pertinent enough to guide the choice of empirical antifungal therapy in ICU

Assessment of pain during labor with pupillometry: a prospective observational study.: Pupillometry and labor pain

International audienceBACKGROUND: Pain intensity is usually self-rated by patients with a numeric rating scale (NRS) but this scale cannot be used for noncommunicating patients. In anesthetized patients, experimental noxious stimulus increases pupillary diameter (PD) and pupillary light reflex amplitude (PLRA), the difference between PD before and after light stimulation. Labor pain is an intense acute nonexperimental stimulus, effectively relieved by epidural analgesia. In this prospective observational study, we therefore describe the effects of labor pain and pain relief with epidural analgesia on PD and PLRA, determine their association with pain intensity and determine the ability of a single measurement of PD or PLRA to assess pain. METHODS: In the first stage, pain (11-point NRS), PD, and PLRA were measured in 4 conditions in 26 laboring women: before and after epidural analgesia and in the presence and absence of a uterine contraction. Pupillometry values among the 4 conditions were compared, and the strength of the association between absolute values of pain and PD or PLRA and between pain and changes in PD or PLRA brought about by uterine contraction was assessed with r(2). In the second stage, 1 measurement was performed in 104 laboring women. The strength of the association between pain and PD or PLRA was assessed with r(2). The ability of PD or PLRA to discriminate pain (NRS > 4) was also assessed. RESULTS: In the first stage, a statistically significant increase in pain, PD, and PLRA was observed during a contraction, and this change was abolished after epidural analgesia. The r(2) for the association between pain and changes in PD (r(2) = 0.25 [95% confidence interval, 0.07-0.46] or PLRA (r(2) = 0.34 [0.14-0.56]) brought about by a uterine contraction was higher than the r(2) for the association between pain and absolute values of PD (r(2) = 0.14 [0.04-0.28]) or PLRA (r(2) = 0.22 [0.10-0.37]) suggesting a stronger association for changes than for absolute values. In the second stage, r(2) was 0.23 [0.10-0.38] for PD and 0.26 [0.11-0.40] for PLRA and the area under the receiver operating characteristics curve was 0.82 [0.73-0.91] and 0.80 [0.71-0.89], respectively. CONCLUSIONS: Changes in PD and PLRA brought about by a uterine contraction may be used as a tool to assess analgesia in noncommunicating patients

Clinical review: Intrapericardial fibrinolysis in management of purulent pericarditis

Purulent pericarditis (PP) is a potentially life-threatening disease. Reported mortality rates are between 20 and 30%. Constrictive pericarditis occurs over the course of PP in at least 3.5% of cases. The frequency of persistent PP (chronic or recurrent purulent pericardial effusion occurring despite drainage and adequate antibiotherapy) is unknown because this entity was not previously classified as a complication of PP. No consensus exists on the optimal management of PP. Nevertheless, the cornerstone of PP management is complete eradication of the focus of infection. In retrospective studies, compared to simple drainage, systematic pericardiectomy provided a prevention of constrictive pericarditis with better clinical outcome. Because of potential morbidity associated with pericardiectomy, intrapericardial fibrinolysis has been proposed as a less invasive method for prevention of persistent PP and constrictive pericarditis. Experimental data demonstrate that fibrin formation, which occurs during the first week of the disease, is an essential step in the evolution to constrictive pericarditis and persistent PP. We reviewed the literature using the MEDLINE database. We evaluated the clinical efficacy, outcome, and complications of pericardial fibrinolysis. Seventy-four cases of fibrinolysis in PP were analysed. Pericarditis of tuberculous origin were excluded. Among the 40 included cases, only two treated by late fibrinolysis encountered failure requiring pericardiectomy. No patient encountered clinical or echocardiographic features of constriction during follow-up. Only one serious complication was described. Despite the lack of definitive evidence, potential benefits of fibrinolysis as a less invasive alternative to surgery in the management of PP seem promising. Early consideration should be given to fibrinolysis in order to prevent both constrictive and persistent PP. Nevertheless, in case of failure of fibrinolysis, pericardiectomy remains the primary option for complete eradication of infection

IGNITE4 : Results of a phase 3, randomized, multicenter, prospective trial of eravacycline vs meropenem in the treatment of complicated intraabdominal infections

Funding Information: Financial support. This work was supported by Tetraphase Pharmaceuticals Inc. Funding Information: Potential conflicts of interest. J. S. S. has received support from Tetraphase Pharmaceuticals Inc. during the production of this manuscript and has served as a consultant to Merck, Pfizer, GlaxoSmithKline, and Melinta outside of the submitted work. A. S received support from Tetraphase Pharmaceuticals Inc. during the production of this manuscript. J. G. received research funding from Tetraphase Pharmaceuticals Inc. for his role as principal investigator of this study. K. L. and L. T. are employed by Tetraphase Pharmaceuticals Inc. D. E. reports grants from Tetraphase Pharmaceuticals Inc. during the conduct of the study and grants from Merck outside of the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Publisher Copyright: © 2018 The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.Background: Increasing antimicrobial resistance among pathogens that cause complicated intraabdominal infections (cIAIs) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae. Methods: IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg every 12 hours or meropenem 1 g every 8 hours intravenously for 4-14 days. The primary objective was to demonstrate statistical noninferiority (NI) in clinical cure rates at the test-of-cure visit (25-31 days from start of therapy) in the microbiological intent-to-treat population using a NI margin of 12.5%. Microbiological outcomes and safety were also evaluated. Results: Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference, -0.5%; 95% confidence interval [CI], -6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified ITT population (231/250 [92.4%] vs 228/249 [91.6%]; difference, 0.8; 95% CI, -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference, 0.8; 95% CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline had relatively low rates of adverse events for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively. Conclusions: Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens. Clinical Trials Registration: NCT01844856.publishersversionPeer reviewe

Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units

CIAR (Club d'infectiologie en Anesthésie-Réanimation) Study Group: Pr B Allaouchiche (HCL, CHU Lyon), Pr C Arich (CHU Nimes), Pr C Auboyer (CHU St-Etienne), Dr JP Caramella (CHG Nevers), Dr JF Cochard (CHU Bordeaux), Dr A Combes (CHG Meaux), Dr P Courant (CHG Avignon), Dr J Durand-Gasselin (CHG Toulon), Pr J Duranteau (APHP, CHU Bicetre), Dr H Floch (CHU Nantes), Dr F Fraisse (CHG St Denis), Pr M Freysz (CHU Dijon), Dr B Garrigues (CHG Aix-en-Provence), Dr B Georges (CHU Toulouse), Pr F Gouin (APHM, CHU Marseille), Pr L Jacob (APHP, CHU St Louis), Pr P Juvin (APHP, CHU Beaujon), Dr J Keinlen (CHU Montpellier), Dr AM Korinek (APHP, CHU Pitie Salpetriere), Dr C Lamer (Institut Mutualiste Montsouris, Paris), Pr JY Lefrant (CHU Nimes), Dr O Lesieur (CHG La Rochelle), Dr Yazine Mahjoub (CHU Amiens), Pr Y Malledant (CHU Rennes), Pr C Martin (APHM, CHU Marseille), Pr O Mimoz (CHU Poitiers), Pr C Paugam-Burtz (APHP, CHU Beaujon, Clichy), Dr PF Perrigault (CHU Montpellier), Pr T Pottecher (CHU Strasbourg), Pr JL Pourriat (APHP, CHU Hotel Dieu), Dr JF Poussel (CHG Metz), Dr A Rabbat (APHP, CHU Hotel Dieu), Dr J Reignier (CHG La Roche sur Yon), Dr P Sichel (CHG Cherbourg), Dr JP Sollet (CHG Argenteuil), Dr D Thevenin (CHG Lens), Dr G Viquesnel (CHU Caen).International audienceINTRODUCTION: Few studies have addressed the decision-making process of antibiotic therapy (AT) in intensive care unit (ICU) patients. METHODS: In a prospective observational study, all consecutive patients admitted over a one-month period (2004) to 41 French surgical (n = 22) or medical/medico-surgical ICUs (n = 19) in 29 teaching university and 12 non-teaching hospitals were screened daily for AT until ICU discharge. We assessed the modalities of initiating AT, reasons for changes and factors associated with in ICU mortality including a specific analysis of a new AT administered on suspicion of a new infection. RESULTS: A total of 1,043 patients (61% of the cohort) received antibiotics during their ICU stay. Thirty percent (509) of them received new AT mostly for suspected diagnosis of pneumonia (47%), bacteremia (24%), or intra-abdominal (21%) infections. New AT was prescribed on day shifts (45%) and out-of-hours (55%), mainly by a single senior physician (78%) or by a team decision (17%). This new AT was mainly started at the time of suspicion of infection (71%) and on the results of Gram-stained direct examination (21%). Susceptibility testing was performed in 261 (51%) patients with a new AT. This new AT was judged inappropriate in 58 of these 261 (22%) patients. In ICUs with written protocols for empiric AT (n = 25), new AT prescribed before the availability of culture results (P = 0.003) and out-of-hours (P = 0.04) was more frequently observed than in ICUs without protocols but the appropriateness of AT was not different. In multivariate analysis, the predictive factors of mortality for patients with new AT were absence of protocols for empiric AT (adjusted odds ratio (OR) = 1.64, 95% confidence interval (95%CI): 1.01 to 2.69), age ≥60 (OR = 1.97, 95% CI: 1.19 to 3.26), SAPS II score >38 (OR = 2.78, 95% CI: 1.60 to 4.84), rapidly fatal underlying diseases (OR = 2.91, 95% CI: 1.52 to 5.56), SOFA score ≥6 (OR = 4.48, 95% CI: 2.46 to 8.18). CONCLUSIONS: More than 60% of patients received AT during their ICU stay. Half of them received new AT, frequently initiated out-of-hours. In ICUs with written protocols, empiric AT was initiated more rapidly at the time of suspicion of infection and out-of-hours. These results encourage the establishment of local recommendations for empiric AT

An Evaluation of the Effectiveness of Risk Minimization Measures for Tigecycline in the European Union

Background: Risk minimization measures (RMM) were implemented from February 2011 in the European Union to address risks of superinfection, off-label use and lack of efficacy associated with tigecycline. The objective of this study was to evaluate RMM effectiveness by describing prescription patterns among adults and children treated with any dose of tigecycline for any indication pre- and post-RMM implementation; incidence proportions of superinfection and lack of efficacy among adults treated with approved doses of tigecycline for complicated intra-abdominal infection and complicated skin and soft tissue infection were also evaluated. Methods: This was an observational, retrospective chart-abstraction study, including charts from 777 patients (399 pre-RMM, 378 post-RMM) at 13 sites across Austria, Germany, Italy, Greece and the United Kingdom (UK). Potential superinfection and lack of efficacy cases among those using tigecycline for on-label indication, age, dose, and duration were adjudicated. The distribution of indications for tigecycline was analyzed overall (i.e. across both study periods) and stratified by study period. Numbers and incidence proportions of superinfection and lack of efficacy cases (potential and adjudicated) were calculated overall and by study period. Results: Off-label use (indication or age) decreased from 54.2% [95% confidence interval (95% CI): 49.0, 59.3%] pre-RMM to 35.7% (95% CI 30.4, 41.2%) post-RMM. Overall, 45.7% (95% CI 41.9, 49.5%) of patients were prescribed tigecycline off-label; the most commonly reported off-label indications were characterized as \u201cother\u201d (25.5%), hospital acquired pneumonia (8.2%), other pneumonia (6.3%), bacteremia (5.2%) and diabetic foot infection (1.5%). Across study periods, incidence proportions of definite or probable superinfection and lack of efficacy in adults treated for approved indications, authorized treatment doses and duration were 4.5% (95% CI 2.1, 8.4%) and 5.5% (95% CI 2.8, 9.7%), respectively. Conclusions: Off-label use of tigecycline decreased following RMM implementation. Overall incidence proportions of definite or probable superinfection and lack of efficacy were low. EU PAS register number: EUPAS3674

Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules.

International audienceAIMS: Carbon monoxide (CO) delivered in a controlled manner to cells and organisms mediates a variety of pharmacological effects to the extent that CO-releasing molecules (CO-RMs) are being developed for therapeutic purposes. Recently, ruthenium-based CO-RMs have been shown to posses important bactericidal activity. Here we assessed the effect of fast CO releasers containing ruthenium (Ru(CO)(3)Cl(glycinate) [CORM-3] and tricarbonyldichlororuthenium(II) dimer [CORM-2]) and a novel slow manganese-based CO releaser ([Me(4)N][Mn(CO)(4)(thioacetate)(2)] [CORM-371]) on O(2) consumption and growth of Pseudomonas aeruginosa (PAO1). We then compared these effects with the action elicited by sodium boranocarbonate (CORM-A1), which lacks a transition metal but liberates CO with a rate similar to CORM-371. RESULTS: CORM-2, CORM-3, and, to a lesser extent, CORM-371 exerted a significant bactericidal effect and decreased O(2) consumption in PAO1 in vitro. The effect appeared to be independent of reactive oxygen species production, but in the case of metal-containing compounds it was prevented by the thiol donor N-acetylcysteine. In contrast, CORM-A1 was bacteriostatic rather than bactericidal in vitro eliciting only a moderate and transient decrease in O(2) consumption. INNOVATION: None of the tested CO-RMs was toxic to murine macrophages or human fibroblasts at the concentration impairing PA01 growth but only ruthenium-containing CO-RMs showed potential therapeutic properties by increasing the survival of mice infected with PA01. CONCLUSION: CO carriers inhibit bacterial growth and O(2) consumption in vitro, but transition metal carbonyls appear more powerful than compounds spontaneously liberating CO. The nature of the metal in CO-RMs also modulates the anti-bacterial effect, with ruthenium-based CO-RMs being efficacious both in vitro and in vivo

Efficacy of tigecycline for the treatment of complicated intraabdominal infections in real-life clinical practice from five european observational studies

Objectives: Tigecycline is a broad-spectrum antibiotic approved for the treatment of complicated intra-abdominal infections (cIAIs). The efficacy of tigecycline when administered as monotherapy or in combination with other antibacterials in the treatment of cIAIs in routine clinical practice is described. Patients and methods: Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). Results: A total of 785 cIAI patients who received tigecycline were included (mean age 63.1+14.0 years). Of these, 56.6% were in intensive care units, 65.6% acquired their infection in hospital, 88.1% had at least one comorbidity and 65.7% had secondary peritonitis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 16.9+7.6 (n=614) and 7.0+4.2 (n=108), respectively, indicating high disease severity. Escherichia coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%) were the most frequently isolated pathogens; 49.1% of infections were polymicrobial and 17.5% were due to resistant pathogens. Overall, 54.8% (n=430) received tigecycline as monotherapy and 45.2% (n=355) as combination therapy for a mean duration of 10.6 days. Clinical response rates at the end of treatment were 77.4% for all patients (567/733), 80.6% for patients who received tigecycline as monotherapy (329/408), 75.2% for patients with a nosocomial infection (354/471), 75.8% for patients with an APACHE II score .15 (250/330) and 54.2% (32/59) for patients with a SOFA score =7. Conclusions: In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cIAI with a high severity of illness