Hospitalisations with infections related to antimicrobial-resistant bacteria from the French nationwide hospital discharge database, 2016.

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.

KPC-Like Carbapenemase-Producing Enterobacteriaceae Colonizing Patients in Europe and Israel.

In a 2008-2011 survey, 17,945 patients in 18 hospital units in Europe and Israel were screened for carriage of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae, resulting in identification of 124 positive patients. The isolates were dominated by Klebsiella pneumoniae sequence type 258 (ST258) KPC-2 and ST512 KPC-3, mainly from Greece and Italy, respectively, whereas Israeli isolates were of diverse species, clones, and KPC variants. Various blaKPC platforms were observed, among which IncFIIK-FIBK plasmids with blaKPC-2/-3 genes in the Tn4401a transposon prevailed.

MLST reveals potentially high-risk international clones of Enterobacter cloacae.

OBJECTIVES: To perform the first multinational Enterobacter cloacae clonality study, using the MLST scheme newly developed in Japan. METHODS: The analysis included 195 rectal carriage E. cloacae isolates resistant to expanded-spectrum cephalosporins (ESCs), collected from patients in 12 hospital units across Europe and Israel. All of the isolates were typed by PFGE and 173 isolates were subjected to MLST. ESC resistance was analysed phenotypically; genes encoding ESBLs and carbapenemases were identified by PCR and sequencing. RESULTS: MLST distinguished 88 STs, which correlated with the PFGE data. PFGE was more discriminatory, producing 129 pulsotypes (169 patterns). Numerous STs were observed in several countries each. The most widespread were ST66, ST78, ST108 and ST114, each having at least 10 isolates from three to five countries, diversified into multiple pulsotypes, with clusters of related isolates in one or more centres. Analysis of the STs against the MLST database revealed several epidemic clonal complexes, such as those with central genotypes ST74 (including ST78) or ST114 (including ST66). ESC resistance was equally related to overexpression of the AmpC cephalosporinase and to ESBL production. Among ESBL producers some spreading subclones were identified, including specific ST66, ST78 and ST114 pulsotypes, associated with CTX-M-15 production. Several isolates produced carbapenemase VIM-1 or KPC-2. CONCLUSIONS: Together with the information available in the MLST database, our results suggest that, like Escherichia coli and Klebsiella pneumoniae, E. cloacae harbours clonal lineages of increased epidemic potential that may be associated with resistance spread.

Phylogenetic lineages, clones and ß-lactamases in an international collection of Klebsiella oxytoca isolates non-susceptible to expanded-spectrum cephalosporins.

OBJECTIVES: The objective of this study was to examine Klebsiella oxytoca clonal and phylogenetic diversity, based on an international collection of carriage isolates non-susceptible to expanded-spectrum cephalosporins (ESCs). METHODS: The study material comprised 68 rectal carriage K. oxytoca isolates non-susceptible to ESCs recovered in 2008-11 from patients in 14 hospitals across Europe and Israel. ESC resistance was tested phenotypically; genes encoding ESBLs, AmpC cephalosporinases and carbapenemases were amplified and sequenced. The isolates were typed by PFGE and MLST, followed by sequencing of blaOXY genes. RESULTS: MLST and PFGE distinguished 34 STs and 47 pulsotypes among the isolates, respectively. Six STs were split into several pulsotypes each. Five STs were more prevalent (n = 2-9) and occurred in several countries each, including ST2, ST9 and ST141, which belong to a growing international clonal complex (CC), CC2. Four phylogenetic lineages were distinguished, each with another type of chromosomal OXY-type ß-lactamase. Three of these, with OXY-1/-5, OXY-2 types and OXY-4, corresponded to previously described phylogroups KoI, KoII and KoIV, respectively. A single isolate from Israel represented a distinct lineage with a newly defined OXY-7 type. The phylogroups showed interesting differences in mechanisms of ESC resistance; KoI strains rarely overexpressed the OXY enzymes but commonly produced ESBLs, whereas KoII strains often were OXY hyperproducers and carried ESBLs much less frequently. AmpCs (DHA-1) and carbapenemases (VIM-1) occurred sporadically. CONCLUSIONS: The study confirmed the high genetic diversity of the collection of K. oxytoca ESC-non-susceptible isolates, composed of phylogroups with distinct types of OXY-type ß-lactamases, and revealed some STs of broad geographical distribution.

Survey of metallo-ß-lactamase-producing Enterobacteriaceae colonizing patients in European ICUs and rehabilitation units, 2008-11.

OBJECTIVES: The objective of this study was to perform a multinational survey of patients' colonization by metallo-ß-lactamase (MBL)-producing Enterobacteriaceae, including their molecular characterization. METHODS: Patients in 18 hospital units across Europe and Israel (n = 17 945) were screened between mid-2008 and mid-2011. MBL-producing isolates were typed by PFGE and MLST. MBL genes were amplified and sequenced within their integrons. Plasmids with MBL genes were analysed by nuclease S1 plus hybridization profiling, mating and transformation assays, and by PCR-based replicon typing. RESULTS: Ninety-one patients in nine centres (six countries), including 62 patients in two Greek ICUs, carried 94 non-duplicate MBL-producing organisms. Klebsiella pneumoniae isolates from Greece dominated (n = 57) and belonged mainly to ST147, ST36 and ST383. All but one of the isolates expressed VIM-1-type MBLs. Isolates of Greek origins produced five enzymes, including new VIM-39, encoded by class 1 integrons of four types. In-e541-like elements prevailed, comprising six variants located on IncR, IncFIIK, IncR + FIIK, IncR + A/C or non-typeable plasmids. The other group were new In4873 and In4863, being the first In416-like elements identified in Greece, which were present on IncA/C or non-typeable plasmids. Isolates from other countries produced only VIM-1 and the major integron was In916, identified in 16 organisms from France, Italy and Spain. In916 was carried by four plasmid types, including IncA/C, IncFIIK and IncHI2. Other integrons included a new element, In3103, in Spain and In110 identified only in Latvia. CONCLUSIONS: This study provided fully comparable data on the occurrence and molecular characteristics of VIM-producing Enterobacteriaceae in a group of hospital units across Europe, documenting recent changes in their epidemiology.

COPD patients with ventilator-associated pneumonia: implications for management.

Data on the occurrence and outcome of patients with chronic obstructive pulmonary disease (COPD) and ventilator-associated pneumonia (VAP) are quite limited. The aim of this study was to determine if COPD intensive care unit (ICU) patients have a higher rate of VAP development, different microbiological aetiology or have worse outcomes than other patients without VAP. A secondary analysis of a large prospective, observational study conducted in 27 European ICUs was carried out. Trauma patients were excluded. Of 2082 intubated patients included in the study, 397 (19.1%) had COPD; 79 (19.9%) patients with COPD and 332 (19.7%) patients without COPD developed VAP. ICU mortality increased by 17% (p < 0.05) when COPD patients developed VAP, remaining an independent predictor of mortality [odds ratio (OR) 2.28; 95% confidence interval (CI) 1.35-3.87]. The development of VAP in COPD patients was associated with a median increase of 12 days in the duration of mechanical ventilation and >13 days in ICU stay (p < 0.05). Pseudomonas aeruginosa was more common in VAP when COPD was present (29.1% vs. 18.7%, p = 0.04) and was the most frequent isolate in COPD patients with early-onset VAP, with a frequency 2.5 times higher than in patients without early-onset VAP (33.3% vs. 13.3%, p = 0.03). COPD patients are not more predisposed to VAP than other ICU patients, but if COPD patients develop VAP, they have a worse outcome. Antibiotic coverage for non-fermenters needs to be included in the empiric therapy of all COPD patients, even in early-onset VAP.

Long-term control of carbapenemase-producing Enterobacteriaceae at the scale of a large French multihospital institution: a nine-year experience, France, 2004 to 2012.

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-Hôpitaux 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<0.001). The number of secondary cases varied significantly depending on the speed and strength of the measures implemented around the CPE index case: quick (within two days of patient admission at the hospital) setting of nursing staff dedicated to the patient, quick setting of simple barrier precautions, or delayed measures of control (p=0.001). A sustained and coordinated strategy can lead to control CPE at the level of a large regional multi-hospital institution in a country where CPE are at an emerging stage.

Comparative population analysis of Klebsiella pneumoniae strains with extended-spectrum ß-lactamases colonizing patients in rehabilitation centers in four countries.

The international project MOSAR was conducted in five rehabilitation centers; patients were screened for rectal carriage of extended-spectrum ß-lactamase (ESBL)-producing members of the Enterobacteriaceae. Among 229 Klebsiella pneumoniae isolates, four clonal groups (CG) or complexes (CC) prevailed: CG17 in France, CG101 in Italy, CG15 in Spain, and CC147 in Israel. ESBLs, mainly CTX-Ms, were produced by 226 isolates; three isolates expressed AmpC-like cephalosporinases. High genetic diversity of K. pneumoniae populations was observed, with specific characteristics at each center.

Clonal structure, extended-spectrum ß-lactamases, and acquired AmpC-type cephalosporinases of Escherichia coli populations colonizing patients in rehabilitation centers in four countries.

The prospective project MOSAR was conducted in five rehabilitation units: the Berck Maritime Hôpital (Berck, France), Fondazione Santa Lucia (Rome, Italy), Guttmann Institute (GI; Barcelona, Spain), and Loewenstein Hospital and Tel-Aviv Souraski Medical Center (TA) (Tel-Aviv, Israel). Patients were screened for carriage of Enterobacteriaceae resistant to expanded-spectrum cephalosporins (ESCs) from admission until discharge. The aim of this study was to characterize the clonal structure, extended-spectrum ß-lactamases (ESBLs), and acquired AmpC-like cephalosporinases in the Escherichia coli populations collected. A total of 376 isolates were randomly selected. The overall number of sequence types (STs) was 76, including 7 STs that grouped at least 10 isolates from at least three centers each, namely, STs 10, 38, 69, 131, 405, 410, and 648. These clones comprised 65.2% of all isolates, and ST131 alone comprised 41.2%. Of 54 STs observed only in one center, some STs played a locally significant role, like ST156 and ST393 in GI or ST372 and ST398 in TA. Among 16 new STs, five arose from evolution within the ST10 and ST131 clonal complexes. ESBLs and AmpCs accounted for 94.7% and 5.6% of the ESC-hydrolyzing ß-lactamases, respectively, being dominated by the CTX-M-like enzymes (79.9%), followed by the SHV (13.5%) and CMY-2 (5.3%) types. CTX-M-15 was the most prevalent ß-lactamase overall (40.6%); other ubiquitous enzymes were CTX-M-14 and CMY-2. Almost none of the common clones correlated strictly with one ß-lactamase; although 58.7% of ST131 isolates produced CTX-M-15, the clone also expressed nine other enzymes. A number of clone variants with specific pulsed-field gel electrophoresis and ESBL types were spread in some locales, potentially representing newly emerging E. coli epidemic strains.

Unsolicited post-prescription antibiotic review in surgical and medical wards: factors associated with counselling and physicians' compliance.

The purpose of this investigation was to describe the impact of an early review of antibiotic prescriptions in a hospital using unsolicited infectious disease physician (IDP) counselling, identify areas for improvement and examine factors associated with physicians' non-compliance. The prescriptions of 15 selected antibiotics from surgical or medical wards were screened daily and reviewed between days 3 and 5 by a single IDP during an 8-month period to identify those likely needing counselling. Improved antibiotic use was sought by encouraging ward physicians to withdraw or de-escalate therapy, promoting oral switch or reducing the duration of therapy whenever appropriate. Variables potentially associated with IDP counselling and physicians' non-compliance were tested using bivariate analysis and then entered in a logistic regression model. Among 857 prescriptions analysed, 54.6 % prompted unsolicited counselling, mostly for stopping therapy (18.8 %), reducing its duration (18.0 %) or de-escalation (13.0 %). Variables independently associated with IDP counselling included antibiotic combination (adjusted odds ratio [aOR], 5.27 [95 % confidence interval (CI), 1.80-15.45]; p = 0.002), non-clinically documented infection (aOR, 4.98 [95 % CI, 2.81-8.82]; p < 0.001) and microbiologically documented infection (aOR, 2.04 [95 % CI, 1.51-2.75]; p < 0.001). The physicians' compliance rate was 77.3 %. Variables independently associated with physicians' non-compliance to the IDP recommendation were the surgical speciality of the ward physician (aOR, 1.91 [95 % CI, 1.17-3.12]; p = 0.009) and advice to reduce the duration of therapy (aOR, 1.88 [95 % CI, 1.12-3.15]; p = 0.017). An unsolicited post-prescription antibiotic review can be successfully implemented with a high rate of physicians' compliance. Areas for targeting improvement measures include prescriptions in surgical wards and shortening the duration of therapy.

Impact of a program combining pre-authorization requirement and post-prescription review of carbapenems: an interrupted time-series analysis.

The objective of this study was to assess the impact on carbapenems use of a program combining pre-authorization requirement and systematic post-prescription review of carbapenems prescriptions. The program was implemented in a 1,230-bed teaching tertiary hospital. Monthly carbapenems consumption was analyzed using a controlled interrupted time-series method and compared to that of vancomycin before and after implementation of the intervention. Compared to the pre-intervention period (14 monthly points), a significant and sustained decrease of carbapenems consumption [1.66 defined daily doses (DDD)/1,000 patient-days; p = 0.048] was observed during the intervention period (12 monthly points), despite an increasing trend in incidence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) isolates (0.02/1,000 patient-days per month; p = 0.093). As expected, vancomycin consumption was unaffected by the intervention. A total of 337 prescriptions were reviewed in the intervention period; most were microbiologically documented (81.3%; ESBL-PE: 39.2%). Three of four (76.6%) carbapenems prescriptions were modified within a median [interquartile range] of 2 [1; 4] days, either after infectious disease physician (IDP) advice (48.4%) or by ward physicians (28.2%). Most changes included de-escalating (52.2%) or reducing the planned duration (22.2%), which resulted in a median duration of treatment of only 3 [2; 7] days. The median length of stay and mortality rate were not influenced by the intervention. This reasonably practicable antimicrobial stewardship program including controlled delivery and systematic reevaluation of carbapenems prescriptions was able to reduce their use in our hospital, despite a rising ESBL-PE incidence.

Factors associated with hospital mortality in community-acquired legionellosis in France.

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.

Culture-based detection of methicillin-resistant Staphylococcus aureus by a network of European laboratories: an external quality assessment study.

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 10(7)-1 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 11-20% to 61-70%. MRSA carriage rates were less variable (0-20%) between countries. Almost all participants (n=22, 96%) screened patients for MRSA carriage during 2009-2010, 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.

Long-term control of vancomycin-resistant Enterococcus faecium at the scale of a large multihospital institution: a seven-year experience.

Repeated outbreaks of vancomycin-resistant Enterococcus faecium (VRE) occurred between 2004 and 2010 in Assistance Publique--Hôpitaux 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<0.001), resulting in a significant trend change of -1.5 cases per month (95% CI: -2.1 to -0.9, p<0.001). The number of cases per outbreak was significantly lower after implementation of the programme. A sustained and coordinated strategy can control emerging bacteria at the level of a large regional multihospital institution.

Adult intensive-care patients with 2009 pandemic influenza A(H1N1) infection.

In France, the surveillance of hospitalized cases of pandemic influenza was implemented in July 2009 and restricted to intensive-care unit (ICU) patients in November. We described the characteristics of the 1065 adult patients admitted to ICUs and analysed risk factors for severe outcome (mechanical ventilation or death). Eighty-seven percent of cases were aged 15-64 years. The case-fatality ratio was 20%. The risk for severe outcome increased with age and obesity while this association was negative for chronic respiratory disease. Late antiviral therapy was associated with a severe outcome in ICU patients with risk factors (adjusted OR 2·0, 95% CI 1·4-3·0). This study confirms the considerable contribution of young adults to A(H1N1) 2009 mortality. It shows the role of obesity as an independent risk factor for severe disease, and of early antiviral therapy as a protective factor, at least in patients with risk factors.

[Severe H1N1 2009 influenza infection in adults: the French experience]. / Formes graves de la grippe H1N1 2009 chez l'adulte: l'expérience française.

The REVA-Flu-SRLF register allowed collection of data from 562 patients infected with H1N1 influenza virus 2009 and hospitalized in the intensive care unit (ICU). The overall mortality of these patients was 20%. The use of invasive ventilation, heart failure, and immunosuppression were associated with mortality. Three hundred forty-one (82%) among the 417 mechanically ventilated patients had an acute respiratory distress syndrome (ARDS). One hundred sixty-nine (30%) had a bacterial co-infection. Corticosteroid therapy was associated with an increased mortality in patients with ARDS. The occupancy rate associated with influenza patients crossed the threshold of 15% in many ICUs.

The effects of topical antibiotics on eradication and acquisition of third-generation cephalosporin and carbapenem-resistant Gram-negative bacteria in ICU patients; a post hoc analysis from a multicentre cluster-randomized trial.

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.

Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.

Healthcare workers' knowledge and perceptions of the risks associated with emerging extensively drug-resistant bacteria.

OBJECTIVE: Guidelines have been issued in 2010 to prevent the spread of emerging extensively resistant bacteria (eXDR), but their implementation is difficult. We aimed to evaluate healthcare workers' (HCW) knowledge and their risk perception to identify barriers to the implementation of guidelines. METHODS: Semi-structured interviews were conducted at a University Hospital, where case patients are regularly admitted. The interviews focused on HCW's knowledge, risk perception, and challenges met. The evaluation of HCW's knowledge and contagiousness and perception of severity of eXDR carriage were analyzed statistically. Risk perception and opinion about guidelines were analyzed by qualitative description. RESULTS: One hundred and twenty-one HCWs were interviewed. The category of HCW, having searched for information on resistant bacteria, and having taken care of case patients were associated with better knowledge. The HCW category, age, type of unit, seniority, and having taken care of case patients were associated with risk perceptions. Qualitative analysis identified 61 themes. HCWs were extremely concerned by the spread of bacteria within the hospital. The main challenges identified were organizational and communication issues. CONCLUSION: HCWs reported a lack of knowledge and a lack of resources to implement guidelines. Strategies to improve guidelines implementation must be based on a better availability of resources, better communication, and new educational methods.