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Antibiotic stewardship requires clear insight into antibiotic overuse and the syndromes that lead to prescription. The aim of this study was to estimate the proportion of antibiotic prescriptions attributable to acute lower respiratory tract infections (LRTIs) during the cold season. Using individual data from the French National Health Insurance (NHI) database, weekly time series were constructed of outpatient antibiotic (beta-lactams and macrolides) prescriptions between January 2010 and December 2017. Time series were also constructed of tenth edition of the International Classification of Diseases (ICD-10) discharge diagnoses from a national network of emergency departments (EDs), stratified by specific syndromes (pneumonia, bronchitis, bronchiolitis and influenza-like illness). The number of outpatient antibiotic prescriptions attributable to these syndromes during the cold season in France was modeled and estimated for the entire population, young children (≤5 years) and the elderly (≥75 years). LRTIs accounted for 40% (95% confidence interval [95% CI]: 29, 52) of outpatient antibiotic use during the cold season for the entire population, including 23% (95% CI: 13, 33) and 17% (95% CI: 13, 22) for bacterial and viral infections, respectively. In children and the elderly, viral LRTIs were the reason for 38% (95% CI: 31, 46) and 20% (95% CI: 16, 25) of outpatient antibiotic use, respectively (with bronchiolitis accountable for half of use in young children). In the entire population and in children, respectively, outpatient antibiotic overuse attributable to viral LRTIs was estimated to be 289 (95% CI: 221, 374) and 1588 (95% CI: 1295, 1922) prescriptions per 100 000 inhabitants per week. These results highlight the major role of viral infections in driving antibiotic prescriptions, particularly in young children.

International audience; Background: The impact of antibiotic resistance (AMR) on initial hospital management has been extensively studied but its consequences after hospital discharge remain largely unknown. We aimed to analyze hospital care trajectories, cumulative length of hospital stays (c-LOS) and associated costs of care over a 1-year period after hospitalization with incident AMR infection.Method: All incident bacterial infection-related hospitalizations occurring from January 1, 2015, to December 31, 2015 and recorded in the French national health data information system were extracted. Bacterial resistance ICD-10 codes determined six infection status. Inpatient and outpatient care consumption and associated costs were studied. The impact of resistance on c-LOS was estimated using a Poisson regression. A sequence analysis through optimal matching method was conducted to identify hospital trajectories along with an extrapolation.Finding: Of the 73,244 patients selected, 15.9% had AMR infection, thus providing 58,286 incident AMR infections after extrapolation. c-LOS was significantly longer for infections with resistant bacteria, reaching 20.4 days and 2.9 additional days IC95%[2.6; 3.2] for skin and soft tissue infections. An estimated 29,793 (51.1%) patients had hospital readmission within the following year, for a total cost of €675 million. Five post-discharge trajectories were identified: Post-hospitalization mainly at home (68.4% of patients); Transition to home from rehabilitation care (12.3%); Early death (

Objectives: The aim was to quantify the effects of selective digestive tract decontamination (SDD) consisting of a mouth paste and gastro-enteral suspension, selective oropharyngeal decontamination with a mouth paste (SOD) and 1-2% chlorhexidine (CHX) mouthwash on eradication and acquisition of carriage of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and carbapenem-resistant Gram-negative bacteria (CR-GNB) in Intensive Care Unit (ICU) patients. Methods: This was a nested cohort study within a cluster-randomized cross-over trial in six European countries and 13 ICUs with 8665 patients. Eradication and acquisition during ICU stay of 3GCR-E and CR-GNB were investigated separately in the rectum and respiratory tract for the three interventions and compared with standard care (SC) using Cox-regression competing events analyses. Results: Adjusted cause specific hazard ratios (CSHR) for eradication of rectal carriage for SDD were 1.76 (95% CI 1.31-2.36) for 3GCR-E and 3.17 (95% CI 1.60-6.29) for CR-GNB compared with SC. For the respiratory tract, adjusted CSHR for eradication of 3GCR-E were 1.47 (0.98-2.20) for SDD and 1.38 (0.92-2.06) for SOD compared with SC, and for eradication of CR-GNB these were 0.77 (0.41- 1.45) for SDD and 0.81 (0.44-1.51) for SOD, compared with SC. Adjusted CSHRs for acquisition of rectal carriage during SDD (compared with SC) were 0.51 (0.40-0.64) for 3GCR-E and of 0.56 (0.40-0.78) for CR-GNB. Adjusted CSHRs for acquiring respiratory tract carriage with 3GCR-E compared with SC were 0.38 (0.28-0.50) for SDD and 0.55 (0.42-0.71) for SOD, and for CR-GNB 0.46 (0.33-0.64) during SDD and 0.60 (0.44-0.81) during SOD, respectively. SOD was not associated with eradication or acquisition of 3GCR-E and CR-GNB in the rectum. Conclusions: Among mechanically ventilated ICU patients, SDD was associated with more eradication and less acquisition of 3GCR-E and CR-GNB in the rectum than SC. SDD and SOD were associated with less acquisition of both 3GCR-E and CR-GNB than SC in the respiratory tract. info:eu-repo/semantics/publishedVersion

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Massive use of antibiotics has led to increased bacterial resistance to these drugs, making infections more difficult to treat. Few studies have assessed the overall antimicrobial resistance (AMR) burden, and there is a paucity of comprehensive data to inform health policies. This study aims to assess the overall annual incident number of hospitalised patients with AMR infection in France, using the National Hospital Discharge database. All incident hospitalisations with acute infections in 2016 were extracted. Infections which could be linked with an infecting microorganism were first analysed. Then, an extrapolation of bacterial species and resistance status was performed, according to age class, gender and infection site to estimate the total number of AMR cases. Resistant bacteria caused 139 105 (95% CI 127 920–150 289) infections, resulting in a 12.3% (95% CI 11.3–13.2) resistance rate. ESBL-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the most common resistant bacteria (>50%), causing respectively 49 692 (95% CI 47 223–52 142) and 19 493 (95% CI 15 237–23 747) infections. Although assumptions are needed to provide national estimates, information from PMSI is comprehensive, covering all acute bacterial infections and a wide variety of microorganisms.

Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, Setting, and Participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum β-lactamase–producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main Outcomes and Measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, −0.6% to 1.1%), 0.6% (95% CI, −0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and Relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care. Trial Registration: ClinicalTrials.gov NCT02208154

Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS). To determine whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen placebo (N = 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO2/FiO2 ≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy. The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54–1.16; p = 0.23]. A post hoc analysis of the 45 patients with hypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06–0.68; p = 0.009]. iNO did not reduce the rate of treatment failure in adult SCD patients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia. NCT00748423.

Defined daily doses (DDD) are the gold standard indicator for quantifying prescriptions. Since 2014, the European Centre for Disease Prevention and Control (ECDC) has also been using the number of packages per 1,000 inhabitants per day (ipd), as a surrogate for prescriptions, to report antibiotic consumption in the community and to perform comparisons between European Union (EU) countries participating in the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). In 2015, consumption was reported to range across Europe from 1.0 to 4.7 packages per 1,000 ipd. Our analysis showed that consumption of antibiotics for systemic use per 1,000 ipd was on average 1.3 times greater in France than in Belgium when considering prescriptions in the numerator, 2.5 times greater when considering packages and 1.2 times greater when considering DDD. As long as the same metrics are used over time, antibiotic consumption data aggregated and disseminated by ECDC are useful for assessing temporal trends at the European level and within individual countries; these data may also be used for benchmarking across EU countries. While DDD - although imperfect - are the most widely accepted metric for this purpose, antibiotic packages do not appear suitable for comparisons between countries and may be misleading.

Resume La maitrise de la diffusion des bacteries multi-resistantes endemiques reste un objectif majeur en France, mais des controverses persistent sur les methodes necessaires a employer pour y parvenir. Plusieurs grandes etudes recentes sont venues cependant eclairer le debat. Une etude controlee de l’isolement/regroupement des patients porteurs de SARM n’a pas montre d’efficacite de cette mesure dans le contexte d’une prevalence tres elevee et d’une observance tres reduite de l’hygiene des mains. L’etude de l’administration des veterans aux Etats-Unis montre un impact notable du depistage systematique associe aux precautions complementaires (PC) sur le taux d’infection a SARM, mais ceux-ci sont associes a d’autres mesures de prevention des infections. L’etude soutenue par le NIH (« STAR-ICU »), de meme que celle sur l’utilisation systematique des « precautions barriere » sont celles dont la methodologie est la plus solide, randomisees en grappes, et ne montrent pas d’effet du depistage et isolement ou du port de gants et blouses systematiques sur la prevention de la transmission des SARM ou d’ERV. La « decontamination » des malades de reanimation par des toilettes systematiques a la chlorhexidine a permis d’obtenir une reduction des taux d’infection a SARM et des bacteriemies, notamment « primaires ». Une grande etude de l’efficacite de la decontamination systematique (sans depistage ni isolement) des malades par toilettes a la chlorhexidine et mupirocine nasale a montre la superiorite de cette strategie sur la reduction des infections a SARM et bacteriemies acquises en reanimation par rapport au depistage et PC en l’absence de decontamination. Enfin, l’etude MOSAR a permis de confirmer l’efficacite du renforcement des precautions standard et de l’hygiene des mains, associee aux toilettes a la chlorhexidine, et l’absence d’apport supplementaire du depistage, meme rapide par PCR, et de l’isolement dans le contexte d’une observance elevee de l’hygiene des mains. Aucune de ces etudes n’a evalue simultanement l’exposition aux antibiotiques.

Twenty-three hospital laboratories from Europe and Israel participated in an external quality assessment (EQA) of the culture-based detection of methicillin-resistant Staphylococcus aureus (MRSA). Participants also reported the MRSA prevalence in clinical cultures and patient screening specimens, as well as the MRSA screening practices employed at their hospitals. An EQA panel of 18 samples consisting of two MRSA harbouring SCCmec IV and I, and one strain each of methicillin-resistant coagulase-negative S. epidermidis, methicillin-sensitive S. aureus and Escherichia coli as pure strains or in mixtures at 1071 cfu absolute loads was analysed by the 23 participants. Seventeen (74%) participants identified 17 or more samples correctly. Of these, 15 (88%) utilised a chromogenic medium alone (ChromID, bioMérieux; BBL CHROMagar, BD Diagnostics; MRSA Select, Bio-Rad Laboratories) or combined with a conventional medium and up to three confirmatory tests. Proportions of MRSA among S. aureus isolated from clinical cultures varied widely, even among hospitals within countries, ranging from 1120% to 6170%. MRSA carriage rates were less variable (020%) between countries. Almost all participants (n = 22, 96%) screened patients for MRSA carriage during 20092010, of which 15 (68%) screened intensive care unit (ICU) patients alone or combined with other targeted high-risk groups, and 10 (45%) combined nasal screening with another body site.

Resume L’usage des carbapenemes va croissant a mesure de l’extension des resistances aux antibiotiques chez les bacilles a Gram negatifs, particulierement des betalactamases a spectre etendu ; il fait craindre la perte d’activite de cette classe, du fait de l’apparition des carbapenemases. Ces recommandations de la Commission des anti-infectieux de l’Assistance publique-Hopitaux de Paris (AP–HP) visent a encourager un usage raisonne et aussi limite que possible des quatre molecules disponibles de la classe, en comparant leurs avantages respectifs et precisant leurs modalites d’utilisation et leurs indications en pratique clinique, ainsi que les alternatives possibles.

Introduction The massive use of antibiotics has led to a significant increase of bacterial resistance to these drugs, making infections more difficult to treat; antimicrobial resistance has become a major public health issue. Few studies have assessed the total burden of antimicrobial resistance, and there is a paucity of comprehensive population-based data. In 2014, because of the impact of antimicrobial resistance on public health, the World Health Organization revised its codification of infections and antimicrobial resistance in the 10th revision of the international classification of diseases (ICD-10), which is used in the French Hospital Discharge Database (PMSI). In France, special attention was given to resistance causing therapeutic difficulties leading to additional specific codes in ICD-10. These improvements are an opportunity to use national healthcare database in order to reduce assumptions and to base burden estimations on actual nationwide data. This study aims to estimate the overall situation of antimicrobial resistance in France based on the PMSI. Methods Study population was incident hospitalizations with an acute infection caused by Streptococcus, Staphylococcus, Enterobacteriaceae or another Gram negative bacteria in 2015. Hospitalizations with infections were identified in the PMSI database from established lists of ICD-10 corresponding to infections, microorganisms and resistances codes. Stays (> 1 day) with an admission between January 1 and December 31, were selected when at least one code of infection was present in principal, related, or significant associated diagnosis. Patients hospitalized with infections in the 12 months preceding the admission were excluded. Using medical-administrative databases for a different objective from their original purpose leads to difficulties, in particular in the context of infectious disease: diagnoses are not related, and some information could be unknown. First, stays were usable only if the infection, the microorganism and the potential resistance could be related. For these stays, bacteria were considered susceptible when no resistance was recorded. Second, if no bacterial species was noted (i.e. because the physician considered irrelevant/unnecessary to obtain microbiological sample or because the culture results may be negative, etc.), the causal agent and its resistance status were extrapolated from the stays with usable information, according to sex, age (7 categories) and site of infection (11 categories). Resulting stays were described, characteristics of infections with resistant bacteria analyzed and the burden of resistance in France estimated. Results In 2015, 979,902 incident hospitalizations with an acute infection were selected. Bacteria species was recorded in 30% of the cases. After extrapolation, it was estimated that bacterial resistance was associated with 111,177 incident infections in France, corresponding to 11.3% of all incident infections. These infections were mostly of the urinary and genital tracts (25.2%), lower respiratory tract (21.1%), gastrointestinal and abdominal (20.7%) and skin and soft tissues infections (14.2%). Among resistant bacteria, the most frequently detected were ESBL-producing Escherichia coli (28.6%), methicillin resistant Staphylococcus aureus (MRSA, 19.9%), and Klebsiella pneumoniae ESBL (5.2%). MRSA and ESBL-producing Enterobacteriaceae (ESBL-PE) were estimated to cause 22,081 and 39,600 infections annually, respectively. Conclusions This study is the first study to evaluate the burden of resistance from a national comprehensive database. Resistance rates among blood infection estimated from the sample (ESBL-PE, MRSA and VRE) were in accordance with those provided by EARS-net, validating the extrapolation. This study also confirms the importance of ESBL-PE and MRSA in the overall burden of resistance.

Objective.We determined the percentage of healthcare workers' (HCWs') hands contaminated with Clostridium difficile spores after caring for patients with C. difficile infection (CDI) and risk factors associated with contamination.Design.Prospective study.Setting.A French university hospital.Methods.We compared the hand contamination rate among HCWs caring for patients with CDI (exposed group; n = 66) with that among an unexposed group (n = 44). Spores of C. difficile were recovered from the hands of HCWs after rubbing their fingers and palms in alcohol shortly after patient care. Associations between hand contamination and HCW category, type (patient or environment), and risk level (high or low risk) of HCW contacts and their respective duration as well as use of gloves were analyzed by bivariate and multivariate analysis.Results.C. difficile spores were detected on 24% of HCWs' hands in the exposed group and on 0% in the unexposed group (P < .001). In the exposed group, logistic regression, which adjusted for high-risk contact (ie, exposure to fecal soiling), contact with the environment, and contact with or without use of gloves, revealed that high-risk contact (adjusted odds ratio [aOR] per 1 contact increment, 2.78; 95% confidence interval [CI], 1.42–5.45; P = .003) and at least 1 contact without use of gloves (aOR, 6.26; 95% CI, 1.27–30.78; P = .02) were independently associated with HCW hand contamination by C. difficile spores.Conclusions.Nearly one-quarter of HCWs have hands contaminated with C. difficile spores after routine care of patients with CDI. Hand contamination is positively associated with exposure to fecal soiling and lack of glove use.

Resume Cette revue generale analyse le risque d’infection chez les malades de reanimation porteurs de staphylocoques dores resistants a la meticilline (SARM), et les consequences des infections a SARM, en evaluant si leur risque de morbi-mortalite, et les couts associes a ces infections different de ceux des infections a germes sensibles. Environ 30 a 50 % des malades porteurs de SARM acquierent une infection. Ce risque augmente avec l’intensite de la colonisation, la rapidite d’acquisition du portage, et avec l’administration d’antibiotiques. Le risque de mortalite des infections a SARM est eleve, mais n’apparait pas superieur a celui des infections a SAMS, sauf peut-etre dans le cas des infections postoperatoires, et leurs consequences en termes de duree de sejour et de couts medicaux sont similaires. Il est cependant evident que s’agissant d’infections secondaires pour une large part a une transmission croisee, les consequences humaines et economiques de l’acquisition de SARM sont tres lourdes et potentiellement evitables.

Resume Les fasciites sont caracterisees par l'atteinte necrosante des fascias, et leurs risques evolutifs, fonctionnel et vital. Un diagnostic precoce, devant des signes cutanes parfois discrets, associes a un syndrome septique (encephalopathie, insuffisance renale, hypotension), permet de commencer la reanimation et decider d'un probable traitement chirurgical. Trois formes principales se distinguent: les fasciites streptococciques, plus souvent monomicrobiennes, parfois associees a un syndrome de ≪ choc toxique streptococcique ≫ (STSS); les fasciites et myosites clostridiennes, souvent polymicrobiennes en cas de plaie associee; enfin, les gangrenes mixtes et ≪ synergistiques ≫, toujours polymicrobiennes (aero-anaerobie). D'autres formes ≪ primitives ≫ de diverses etiologies, habituellement monomicrobiennes, surviennent sur des terrains particuliers. Le pronostic depend de l'âge, des comorbidites, et surtout de la gravite du syndrome septique et de son expression. La reanimation initiale est dominee par le traitement de l'etat septique, avec une composante hypovolemique marquee. Le traitement antibiotique de reference est la penicilline G pour les formes streptococciques et clostridiennes; il comporte une association active sur les enterobacteries, les streptocoques et enterocoques et les anaerobies (incluant les Bacteroides ) dans les autres cas ou les cas d'etiologie incertaine. Dans les formes avec choc toxinique, l'association a la penicilline de clindamycine ou de rifampicine est recommandee, pour leur activite sur la production d'exotoxines; l'administration d'immunoglobulines non specifiques apparait egalement utile. L'interet de l'oxygenotherapie hyperbare n'est pas demontre. La prevention des complications de la reanimation prolongee comporte en particulier la prise en charge precoce du deficit nutritionnel preexistant ou rapidement installe, et la prevention des accidents thrombo-emboliques frequents.

In a randomized trial conducted in 27 intensive care units, we compared the clinical efficacy and safety of piperacillin-tazobactam (TAZ; 4 g/0.5 g q.i.d.) and of ceftazidime (CAZ; 1 g q.i.d.), both combined with amikacin (7.5 mg/kg b.i.d.), as therapy for ventilator-associated pneumonia (VAP; acquired after > or =48 hours of mechanical ventilation). VAP was diagnosed with use of protected samples and quantitative cultures, and outcome was assessed blindly from treatment. Of 204 patients suspected of having VAP and randomized to a treatment arm of the study, 127 (64%) had bacteriologically confirmed infections, of which 37% were polymicrobial and 32% involved Pseudomonas aeruginosa; 115 patients (51 TAZ and 64 CAZ recipients) remained evaluable as per protocol. Clinical/bacteriologic cure rates (TAZ vs. CAZ, 51% vs. 36%; 95% confidence interval of difference, -0.2% to 30.2%), and 28-day mortality rates (16% vs. 20%) were similar; however, fewer bacteriologic failures occurred with TAZ (33% vs. 51%; P = .05). We conclude that the two regimens were of equivalent clinical efficacy in therapy for confirmed VAP.

The study aims were: (i) to define the prevalence of and risk factors for colonization by extended spectrum β-lactamase (ESBL) -producing Enterobacteriaceae (EPE) among healthcare workers (HCWs) and family members (FMs) of EPE-colonized patients in rehabilitation units and (ii) to compare EPE isolates from these three groups. The study included 286 FMs of 194 EPE-carrying patients identified in five rehabilitation units located in Israel, Italy, France and Spain. The EPE were detected in rectal swabs from 26 (9%) of 286 FMs screened. In multivariate analyses, older age of FM, greater mean number of hours spent with the patient, being a daughter or a female spouse of a patient, and chronic lung disease of the patient were significantly associated with carriage in the FM. Escherichia coli was the most common organism (76%), followed by Klebsiella pneumoniae (19%). Isolates were typed by pulsed field gel electrophoresis and multilocus sequence typing, and ESBLs were identified by PCR sequencing. A comparison of paired species isolates from FMs and their respective patient showed that 17 of 23 strains were indistinguishable. EPE were detected in 35 (3.5%, E. coli = 34) of the 1001 HCWs screened. Feeding patients was associated with EPE carriage by HCWs. Only 7 of 23 E. coli subclones cultured from HCWs were also represented among 376 patient-derived ESBL-producing E. coli isolates from the same rehabilitation units. In Spain, a higher proportion of HCWs and FMs were ESBL carriers than elsewhere (p

Repeated outbreaks of vancomycin-resistant Enterococcus faecium (VRE) occurred between 2004 and 2010 in Assistance Publique--Hopitaux de Paris (AP-HP), a 23,000-bed multi-hospital institution. From August 2004 to December 2005, the French guidelines for preventing cross-transmission of multiresistant bacteria were applied. Because the number of VRE cases continued to increase, an institutional control programme was implemented from January 2006 onwards: it foresees stopping transfer of VRE and contact patients, separating VRE and contact patients in distinct cohorts, intervention of a central infection control team to support local teams, and quick application of measures as soon as first VRE cases are identified. Between August 2004 and December 2010, 45 VRE outbreaks occurred in 21 of the 38 AP-HP hospitals, comprising 533 cases. Time series analysis showed that the mean number of cases increased by 0.8 cases per month (95% confidence interval (CI): 0.3 to 1.3, p=0.001) before, and decreased by 0.7 cases per month after implementation of the programme (95% CI: -0.9 to -0.5, p

Empirical broad spectrum antimicrobial therapy prescribed in life-threatening situations should be de-escalated to mitigate the risk of resistance emergence. Definitions of de-escalation (DE) vary among studies, thereby biasing their results. The aim of this study was to provide a consensus definition of DE and to establish a ranking of β-lactam according to both their spectra and their ecological consequences. Twenty-eight experts from intensive care, infectious disease and clinical microbiology were consulted using the Delphi method (four successive questionnaires) from July to November 2013. More than 70% of similar answers to a question were necessary to reach a consensus. According to our consensus definition, DE purpose was to reduce both the spectrum of antimicrobial therapy and the selective pressure on microbiota. DE included switching from combination to monotherapy. A six-rank consensual classification of β-lactams allowing gradation of DE was established. The group was unable to differentiate ecological consequences of molecules included in group 4, i.e. piperacillin/tazobactam, ticarcillin/clavulanic acid, fourth-generation cephalosporin and antipseudomonal third-generation cephalosporin. Furthermore, no consensus was reached on the delay within which DE should be performed and on whether or not the shortening of antibiotic therapy duration should be included in DE definition. This study provides a consensual ranking of β-lactams according to their global ecological consequences that may be helpful in future studies on DE. However, this work also underlines the difficulties of reaching a consensus on the relative ecological impact of each individual drug and on the timing of DE.

There are few topics that have been subjected to such controversy as the question of the influence of nosocomial infections on outcomes, especially mortality, of critically ill patients. The topic is indeed of importance, since nosocomial infection (similarly to other iatrogenic* events) is a frequent event [1, 2, 3] and probably the most frequent drawback of intensive care, and determining outcomes attributable to nosocomial intensive care unit (ICU)-acquired infections is going to bear heavily on the design and interpretation of studies aimed at prevention or treatment of such infections. Therefore, the question whether prevention of nosocomial infection will result, or not, in improved outcome from intensive care is undermined by the uncertainty surrounding the consequences of infection on outcome. For example, it is apparent that if nosocomial infections do not influence mortality, there is no point in attempting to show a difference in mortality through implementation of a preventive or therapeutic intervention. In this circumstance, the impact of the intervention on other end-points such as length of stay or antibiotic use will be examined, and this has important imphcations in terms of study design and sample size needed. In this chapter, we shall examine the available data for the most common nosocomial infections occurring in ICU patients, in terms of their impact on mortality, length of stay and resource use, including antibiotics when available. Most such studies have focused on specific sites of infection, and these will be examined separately, after a brief overview of the problem. We shall then examine the evidence, if any, regarding to what extent preventing nosocomial infection may impact on outcome of critically ill patients, and the indicators that may be used for the purpose of quality improvement processes and follow-up.

Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4 and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial partial pressure of O2 (PaO2)/fraction of inspired O2 (FIO2) during mechanical ventilation. The severity of lung injury in the two models was clearly different, since PaO2/FIO2 were approximately 400 mmHg in PYO- and LPS-induced injuries, respectively. Both contrast, alveolar neutrophil influx, unstimulated oxygen metabolite production, and proteinase (elastase, gelatinase B) secretions of ex vivo alveolar PMNs were not larger in the PYO model. Thus the difference in severity was not associated with variations in alveolar neutrophil recruitment or activation. Moreover, gelatinase and leukocyte elastase activities were absent in bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar spaces. We conclude that alveolar neutrophils are not sufficient to create severe respiratory failure.

A clear understanding of which patients acquire nosocomial infection and why they do it is an important goal to improve infection control measures and design preventive strategies adapted to the various at-risk populations entering our ICU. For example, it is now clear that prevention of pneumonia through administration of selective digestive decontamination (SDD) to all unselected ICU patients is a poorly effective exercise, wasteful of resources, and potentially harmful. Selected populations of patients who combine specific risk factors may however benefit from this preventive technique or some of its components.

To define the most important diagnostic signs, symptoms and laboratory findings related to intra-abdominal sepsis in the early post-operative period, 15 binary variables were prospectively assessed in 100 febrile (> 39 °C) post-laparotomy patients admitted to an intensive care unit. Intra-abdominal sepsis was found alone in 55 patients and in association with an extra-abdominal focus in 11 patients. Fever was related to an extra-abdominal septic focus in 23 patients and no infectious cause was found in 11. Analysis (χ2) indicated that 6 of the 15 variables were significantly associated with an intra-abdominal focus of infection. The predictive value of each variable, indicated by relative risk, ranked the six variables in order of diagnostic importances: no bacteraemia (1·67), leucocytosis (1·60), ileus (1·50), mental disturbances (1·41), contaminated first laparotomy (1·38), abdominal tenderness (1·22). The absence of bacteraemia was the most important finding separating intra- and extra-abdominal foci of infection. In a febrile post-laparotomy patient with any evidence of sepsis, the absence of bacteraemia should not lull the physician into a false sense of security but rather alert him to the likelihood of an intra-abdominal septic focus.

We evaluated the antithrombotic efficacy of the low molecular weight heparin (LMWH) fraction PK 10169 in nine consecutive patients with acute pulmonary embolism documented by pulmonary angioscan and angiography. Therapy with PK 10169 was initiated by an i.v. bolus of 0.5 mg/kg, followed by a continuous intravenous infusion during the first 10 days; the drug was then given subcutaneously twice daily during the following 15 days. The dosage of PK 10169 was adjusted by daily measurements of anti-Xa and anti-IIa activities using amidolytic methods. For a dosage ranging from 1.4 to 4.1 mg/kg per day during the i.v. period and from 0.7 to 3.5 mg/kg per day during the s.c. period, the anti-Xa activity ranged from 4 to 8.7 PK U/ml and from 4.5 to 7.2 PK U/ml respectively. Clinical improvement was observed in all the patients and was consistent with progressive reperfusion evaluated by successive angioscans. No recurrence of pulmonary embolism occurred. No deleterious hemorrhagic side-effects were observed, even in two patients at high risk of bleeding. In this pilot study, the LMWH fraction PK 10169 proved to be an effective anticoagulant therapy during the first three weeks after pulmonary embolism in man.

In 2009, following the occurrence of several outbreaks of carbapenemase-producing Enterobacteriaceae (CPE), a programme for controlling the spread of CPE was implemented in the 38 hospitals of the Assistance Publique-Hopitaux de Paris, a 21,000-bed institution. This programme included recommendations to isolate, and screen for CPE, patients previously hospitalised abroad, and bundled measures to control cross transmission (barrier precautions, dedicated staff and screening of contact patients). From 2004 to 2012, 140 CPE index cases were identified, 17 leading to outbreaks. After application of the programme, in spite of an increase in the number of CPE index cases epidemiologically linked with a recent stay or hospitalisation abroad, the proportion of cases followed by outbreaks, which was 40% (4/10) before 2009, decreased to 10% (13/130) (p=0.02), and the proportion of secondary cases among all CPE cases decreased from 69% (22/32) to 23% (38/168), (p

Controversies regarding control of endemic methicillin-resistant Staphylococcus aureus (MRSA) stem in part from the paucity of data available on the actual costs of implementing MRSA control strategies.