[Show abstract][Hide abstract] ABSTRACT: Infective endocarditis (IE) due to gram-negative bacilli (GNB) is rare. However, several studies described a change in the epidemiological profile of patients within the past few years.
We reviewed all cases diagnosed and followed in the infectious diseases ward of a French teaching hospital in Paris between 2009 and 2014, inclusive.
Among the 17 patients with definite GNB-IE (11 male, mean age 54 years), 12 (70%) were due to non-HACEK GNB and 5 (30%) to HACEK group GNB. A prosthetic valve was involved in 10 cases (8 in non-HACEK and 2 in HACEK group). Escherichia coli (4/12 patients) and Pseudomonas aeruginosa (3/12 patients) were the most common pathogens in the first group; all the pathogens in the second group were Haemophilus spp. One-third of the patients with non-HACEK GNB had nosocomial IE, whereas injection drug use-related infections were rare (2/12). All patients with HACEK infection had at least one complication (intracardiac abscess, stroke or other systemic embolization). All patients were treated by antibiotic combination therapy during a median time of 42 days (interquartile range (IQR) = 42-42) and 10 (59%) underwent cardiac surgery. One death at 9 months was observed in the non-HACEK group.
Regarding HACEK IE, this report supports the frequent association with vascular complications. Regarding non-HACEK GNB IE, this report supports the increasing proportion of nosocomial infections. We reported a high proportion of surgery in the therapeutic management of both HACEK and non-HACEK groups associated with no in-hospital mortality.
[Show abstract][Hide abstract] ABSTRACT: Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.
Intensive Care Medicine 06/2015; DOI:10.1007/s00134-015-3853-7 · 7.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known. Methods. From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier. Results. Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return. Conclusions. MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond. Clinical Trials Registration. NCT01526187.
[Show abstract][Hide abstract] ABSTRACT: Aims
Modifications of antimicrobials’ pharmacokinetic parameters have been reported in critically ill patients, resulting in a risk of treatment failure. We characterized amikacin pharmacokinetic variability in critically ill patients with ventilator-associated pneumonia (VAP) and evaluated several dosing regimens.
We conducted a prospective multicenter study in critically ill patients with presumptive diagnosis of Gram-negative bacilli (GNB) VAP. Patients empirically received imipenem and a single-dose of amikacin, which was administered as a 30-min infusion (20 mg/kg). Concentrations were measured 0.5, 1, 8, 16, and 24 h after beginning of infusion. Pharmacokinetic parameters were estimated using a population approach. Main pharmacodynamic target was a ratio ≥10 between the concentration achieved 1 h after beginning of infusion (C
1h) and the minimal inhibitory concentration of the liable bacteria (MIC). We simulated individual C
1h for several dosing regimens by Monte Carlo method and computed C
1h/MIC ratios for MICs from 0.5 to 64 mg/L.
Sixty patients (47 males), median (range) age, and body weight, 61.5 years (28–84) and 78 kg (45–126), respectively, were included. Amikacin median C
1h was 45 mg/L (22–87). Mean value (between-patients variability) for CL, V1, Q, and V2 were 4.3 L/h (31 %), 15.9 L (22 %), 12.1 L/h (27 %), and 21.4 L (47 %), respectively. CL increased with CrCL (p
European Journal of Clinical Pharmacology 10/2014; DOI:10.1007/s00228-014-1766-y · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsSignificant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator-associated pneumonia and evaluate several dosage regimens. Methods
This French multicentre, prospective, open-label study was conducted in ICU patients with a presumptive diagnosis of ventilator-associated pneumonia caused by Gram-negative bacilli, who empirically received imipenem intravenously every 8h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000mg with administration every 6 or 8h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%. ResultsFifty-one patients were included in the PK analysis. Imipenem concentration data were best described by a two-compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between-subject variability) was 13.2lh(-1) (38%) and estimated central volume 20.4l (31%). At an MIC of 4gml(-1), the probability of achieving 40% fractional time > MIC was 91.8% for 0.5h infusions of 750mg every 6h, 86.0% for 1000mg every 8h and 96.9% for 1000mg every 6h. Conclusions
This population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750mg every 6h and not 1000mg every 8h.
British Journal of Clinical Pharmacology 06/2014; 78(5). DOI:10.1111/bcp.12435 · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe the prevalence of carriage and variables associated with introduction of highly drug-resistant microorganisms (HDRMO) into a French hospital via patients repatriated or recently hospitalized in a foreign country. The prevalence of HDRMO was 11% (15/132), with nine carbapenamase-producing Enterobacteria-ceae, nine carbapenem-resistant Acinetobacter baumannii and six glycopeptide-resistant enterococci. Half of the admitted patients (63/132, 48%) were colonized with extended spectrum beta-lac-tamase-producing Enterobacteriaceae (ESBLPE). Among the four episodes with secondary cases, three involved A. baumannii.
[Show abstract][Hide abstract] ABSTRACT: We retrospectively studied daptomycin use during 2010 at the Bichat-Claude-Bernard teaching-hospital (Paris) to observe the evolution of daptomycin prescriptions.
Twenty-one patients were included and several parameters were documented: site of infection, bacterial species involved, reason for daptomycin use, dose and clinical outcome.
Ninety-five percent of daptomycin prescritions were off-label and most did not comply with local guidelines. Fifteen of the 21 patients were cured (71%), including 9 patients of the 12 with off-label and off-local recommendation prescriptions (75%). Osteitis and Enterococcus spp endocarditis were the new indications. Daptomycin was increasingly used at higher doses: 52% of our patients were given doses above 6mg/kg. Staphylococcus spp. was the most frequent pathogen responsible for infection is our patients, followed by Enterococcus spp.
Daptomycin use is likely to evolve because of its effectiveness in the treatment of osteitis, left-sided and Enterococcus spp. infective endocarditis. It is generally used at higher doses, which are well tolerated. However, therapeutic monitoring needs to be developed. The antibiotic commission of our hospital gave new recommendations for daptomycin use in 2011.
[Show abstract][Hide abstract] ABSTRACT: The increasing prevalence of extended spectrum beta-lactamase producing enterobacteriaceae (ESBLPE) requires defining the use of carbapenems in first intention. We analyzed the associations between enterobacteriaceae bacteremia (EbBact) and ESBLPE carriage during 10 years in a 950-bed teaching hospital.
We analyzed a 10-year (July 2001 to June 2011) prospective collection of bacteremia cases including 2 databases: (1) EbBact and (2) a computerized database of patients carrying EBLSE. Only one episode of EbBact was analyzed per patient and hospital stay. Factors associated with ESBLPE bacteremia were assessed by univariate and multivariate logistic regression analysis.
Overall, 2355 cases of EbBact were identified, among which 135 (5.7%) were ESBLPE (2001-05: 1.4%, 2006-09: 7.6%, 2010-11: 14.2%). ESBLPE bacteremia was observed in 52 of the 88 (59%) patients carrying ESBLPE and in 83/2267 (3.7%) patients not known to be colonized with ESBLPE. Factors associated with ESBLPE bacteremia in patients not known to be colonized were: female gender (ORa=0.56, CI95% [0.34-0.91]), hospitalization in the ICU (ORa=2.51 [1.27-5.05]) or medical/surgical wards (ORa=1.83 [1.04-3.38]), the period (2006-09, ORa=4.08 [2.21-8.16]; 2010-11, ORa=8.17 [4.14-17.06] compared to 2001-05), and history of EbBact (ORa=2.29 [0.97-4.79]).
In case of EbBact, patients known to be colonized with ESBLPE present with ESBLPE bacteremia in more than half of the cases, requiring carbapenems as empirical antibiotic treatment. The global prevalence of ESBLPE among patients presenting with EbBact not known to be colonized with ESBLPE was 3.7%.
[Show abstract][Hide abstract] ABSTRACT: According to French national recommendations, the detection of a patient colonized with glycopeptide-resistant enterococci (GRE) leads to interruption of new admissions and transfer of contact patients (CPs) to another unit or healthcare facility, with weekly screening of CPs.
We evaluated the medical and economic impact of a pragmatic adaptation of national guidelines associated with a real-time PCR (RTP) (Cepheid XpertTM vanA/vanB) as part of the strategy for controlling GRE spread in two medical wards. Screening was previously performed using chromogenic selective medium (CSM). Turn around time (TAT), costs of tests and cost of missed patient days were prospectively collected. In February 2012, the identification of GRE in one patient in the diabetology ward led to the screening of 31 CPs using CSM; one secondary case was identified in a CP already transferred to the Nephrology ward. Awaiting the results of SCM (median TAT, 70.5 h), 41 potential patient days were missed, due to interruption of admissions. The overall cost (screening tests + missing patient.days) was estimated at 14, 302.20 [euro sign]. The secondary case led to screening of 22 CPs in the Nephrology ward using RTP. Because of a short median TAT of 4.6 h, we did not interrupt admissions and patients' transfers. Among 22 CPs, 19 (86%) were negative for vanA, 2 were positive for vanB and 3 had invalid results needing CSM. The overall cost of the strategy was estimated at 870.40 [euro sign] (cost of screening tests only), without missing patient days.
The rapid PCR test for vanA-positive GRE detection both allowed rapid decision about the best infection control strategy and prevented loss of income due to discontinuation of patient transfers and admissions.