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1.  Minimizing antibiotic exposure in the ICU: in search of the optimal strategy 
Critical Care  2014;18(5):613.
The current paradigm for antibiotic management in critically ill patients is to initiate broad-spectrum therapy followed by de-escalation based on microbiological results. Routine screening cultures may allow better targeting and reduce unnecessary exposure to antibiotics.
doi:10.1186/s13054-014-0613-y
PMCID: PMC4330599  PMID: 25672663
2.  Unrevealing culture-negative severe sepsis 
Critical Care  2013;17(5):1001.
Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic challenges to both clinicians and microbiologists and further questions the validity of sepsis definitions.
doi:10.1186/cc13022
PMCID: PMC4056359  PMID: 24074289
3.  Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: a prospective cohort study, systematic review and individual patient data meta-analysis 
Critical Care  2014;18(2):R44.
Introduction
Procalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza.
Methods
Clinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search.
Results
PCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 μg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 μg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 μg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder.
Conclusions
In critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment.
doi:10.1186/cc13760
PMCID: PMC4056761  PMID: 24612487
4.  Duration of colonization with antimicrobial-resistant bacteria after ICU discharge 
Intensive Care Medicine  2014;40(4):564-571.
Purpose
Readmission of patients colonized with antimicrobial-resistant bacteria (AMRB) is important in the nosocomial dynamics of AMRB. We assessed the duration of colonization after discharge from the intensive care unit (ICU) with highly resistant Enterobacteriaceae (HRE), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE).
Methods
Data were obtained from a cluster-randomized trial in 13 ICUs in 8 European countries (MOSAR-ICU trial, 2008–2011). All patients were screened on admission and twice weekly for AMRB. All patients colonized with HRE, MRSA, or VRE and readmitted to the same ICU during the study period were included in the current analysis. Time between discharge and readmission was calculated, and the colonization status at readmission was assessed. Because of interval-censored data, a maximum likelihood analysis was used to calculate the survival function, taking censoring into account. A nonparametric two-sample test was used to test for differences in the survival curves.
Results
The MOSAR-ICU trial included 14,390 patients, and a total of 64,997 cultures were taken from 8,974 patients admitted for at least 3 days. One hundred twenty-five unique patients had 141 episodes with AMRB colonization and at least 1 readmission. Thirty-two patients were colonized with two or more AMRBs. Median times until clearance were 4.8 months for all AMRB together, 1.4 months for HRE, <1 month for MRSA, and 1.5 months for VRE. There were no significant differences between the survival curves.
Conclusion
Fifty percent of the patients had lost colonization when readmitted 2 or more months after previous ICU discharge.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134-014-3225-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s00134-014-3225-8
PMCID: PMC3969519  PMID: 24522879
Antimicrobial-resistant bacteria; ICU; Colonization; Survival function; Interval censored data
5.  Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial 
The Lancet Infectious Diseases  2014;14(1):31-39.
Summary
Background
Intensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs.
Methods
We did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12–15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638.
Findings
Seven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954–0·999) for phase 2 and 1·015 (0·998–1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676–1·348) for phase 2 and 0·634 (0·349–1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890–0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06).
Interpretation
Improved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing.
Funding
European Commission.
doi:10.1016/S1473-3099(13)70295-0
PMCID: PMC3895323  PMID: 24161233
6.  Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors 
Critical Care  2013;17(6):R269.
Introduction
We assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF).
Methods
This is an observational cohort study using data prospectively collected over a three-year period in a medical ICU of a university hospital.
Results
Among 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO2/FiO2 >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation.
Conclusions
With intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO2/FiO2 > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality.
doi:10.1186/cc13103
PMCID: PMC4057073  PMID: 24215648
7.  Comparison of strategies to reduce meticillin-resistant Staphylococcus aureus rates in surgical patients: a controlled multicentre intervention trial 
BMJ Open  2013;3(9):e003126.
Objective
To compare the effect of two strategies (enhanced hand hygiene vs meticillin-resistant Staphylococcus aureus (MRSA) screening and decolonisation) alone and in combination on MRSA rates in surgical wards.
Design
Prospective, controlled, interventional cohort study, with 6-month baseline, 12-month intervention and 6-month washout phases.
Setting
33 surgical wards of 10 hospitals in nine countries in Europe and Israel.
Participants
All patients admitted to the enrolled wards for more than 24 h.
Interventions
The two strategies compared were (1) enhanced hand hygiene promotion and (2) universal MRSA screening with contact precautions and decolonisation (intranasal mupirocin and chlorhexidine bathing) of MRSA carriers. Four hospitals were assigned to each intervention and two hospitals combined both strategies, using targeted MRSA screening.
Outcome measures
Monthly rates of MRSA clinical cultures per 100 susceptible patients (primary outcome) and MRSA infections per 100 admissions (secondary outcome). Planned subgroup analysis for clean surgery wards was performed.
Results
After adjusting for clustering and potential confounders, neither strategy when used alone was associated with significant changes in MRSA rates. Combining both strategies was associated with a reduction in the rate of MRSA clinical cultures of 12% per month (adjusted incidence rate ratios (aIRR) 0.88, 95% CI 0.79 to 0.98). In clean surgery wards, strategy 2 (MRSA screening, contact precautions and decolonisation) was associated with decreasing rates of MRSA clinical cultures (15% monthly decrease, aIRR 0.85, 95% CI 0.74 to 0.97) and MRSA infections (17% monthly decrease, aIRR 0.83, 95% CI 0.69 to 0.99).
Conclusions
In surgical wards with relatively low MRSA prevalence, a combination of enhanced standard and MRSA-specific infection control approaches was required to reduce MRSA rates. Implementation of single interventions was not effective, except in clean surgery wards where MRSA screening coupled with contact precautions and decolonisation was associated with significant reductions in MRSA clinical culture and infection rates.
Trial registration
clinicaltrials.gov identifier: NCT00685867
doi:10.1136/bmjopen-2013-003126
PMCID: PMC3780302  PMID: 24056477
Infection Control < Infectious Diseases; Surgery
8.  Role of biomarkers in the management of antibiotic therapy: an expert panel review: I – currently available biomarkers for clinical use in acute infections 
In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics.
doi:10.1186/2110-5820-3-22
PMCID: PMC3708786  PMID: 23837559
Infection; Sepsis; Emergency medicine; Biomarkers; Procalcitonin; C-reactive protein; sTREM-1; suPAR; proADM; Presepsin
9.  Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy 
Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (<0.25 ng/mL); in patients having nosocomial LRTI, data are insufficient to recommend initiating therapy based on a single PCT level or even repeated measurements. For children with suspected bacterial meningitis, we recommend using a decision rule as an aid to therapeutic decisions, such as the Bacterial Meningitis Score or the Meningitest®; a single PCT level ≥0.5 ng/mL also may be used, but false-negatives may occur. In adults with suspected bacterial meningitis, we suggest integrating serum PCT measurements in a clinical decision rule to help distinguish between viral and bacterial meningitis, using a 0.5 ng/mL threshold. For ICU patients suspected of community-acquired infection, we do not recommend using a threshold serum PCT value to help the decision to initiate antibiotic therapy; data are insufficient to recommend using PCT serum kinetics for the decision to initiate antibiotic therapy in patients suspected of ICU-acquired infection. In children, CRP can probably be used to help discontinue therapy, although the evidence is limited. In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has been obtained. For ICU patients who have nonbacteremic sepsis from a known site of infection, antibiotics can be stopped if the PCT level at day 3 is < 0.5 ng/mL or has decreased by >80% relative to the highest level recorded, irrespective of the severity of the infectious episode; in bacteremic patients, a minimal duration of therapy of 5 days is recommended.
doi:10.1186/2110-5820-3-21
PMCID: PMC3716933  PMID: 23830525
Infection; Sepsis; Emergency medicine; Biomarkers; Procalcitonin; C-reactive protein; Pancreatitis; Meningitis; Pneumonia
10.  Vascular purpura revealing a severe dilated cardiomyopathy with left ventricular apical thrombus 
We present a case of vascular purpura revealing an intra-cardiac left-sided thrombus complicating an end-stage dilated cardiomyopathy. Vascular purpura main etiologies encompass the wide specturm of vasculitides and microvascular-occlusion syndromes. Among them, cardiac embolism represents an unusal but potentially severe etology.
doi:10.4103/0975-3583.102724
PMCID: PMC3516016  PMID: 23233780
Cardiogenic shock; cardiomyopathy; dilated; leukocytoclastic; purpura; vasculitis
11.  Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic 
Critical Care  2012;16(4):R118.
Introduction
The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs.
Methods
We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden.
Results
Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas.
Conclusions
The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.
doi:10.1186/cc11412
PMCID: PMC3580695  PMID: 22776231
12.  Impact of Antibiotic Exposure Patterns on Selection of Community-Associated Methicillin-Resistant Staphylococcus aureus in Hospital Settings▿† 
Antimicrobial Agents and Chemotherapy  2011;55(10):4888-4895.
Community-associated methicillin-resistant S. aureus (CA-MRSA) is increasingly common in hospitals, with potentially serious consequences. The aim of this study was to assess the impact of antibiotic prescription patterns on the selection of CA-MRSA within hospitals, in a context of competition with other circulating staphylococcal strains, including methicillin-sensitive (MSSA) and hospital-associated methicillin-resistant (HA-MRSA) strains. We developed a computerized agent-based model of S. aureus transmission in a hospital ward in which CA-MRSA, MSSA, and HA-MRSA strains may cocirculate. We investigated a wide range of antibiotic prescription patterns in both intensive care units (ICUs) and general wards, and we studied how differences in antibiotic exposure may explain observed variations in the success of CA-MRSA invasion in the hospitals of several European countries and of the United States. Model predictions underlined the influence of antibiotic prescription patterns on CA-MRSA spread in hospitals, especially in the ICU, where the endemic prevalence of CA-MRSA carriage can range from 3% to 20%, depending on the simulated prescription pattern. Large antibiotic exposure with drugs effective against MSSA but not MRSA was found to promote invasion by CA-MRSA. We also found that, should CA-MRSA acquire fluoroquinolone resistance, a major increase in CA-MRSA prevalence could ensue in hospitals worldwide. Controlling the spread of highly community-prevalent CA-MRSA within hospitals is a challenge. This study demonstrates that antibiotic exposure strategies could participate in this control. This is all the more important in wards such as ICUs, which may play the role of incubators, promoting CA-MRSA selection in hospitals.
doi:10.1128/AAC.01626-10
PMCID: PMC3187008  PMID: 21788461
13.  Twenty years of antimicrobial resistance control programme in a regional multi hospital institution, with focus on emerging bacteria (VRE and CPE) 
Background
Assistance Publique-Hôpitaux de Paris (APHP), the largest public health care institution in France (38 hospitals, 23,000 beds, serving 11.6 millions inhabitants) launched in 1993 a long term programme to control and survey multidrug resistant bacteria (MDR).
Findings
AP-HP MDR programme consisted in successive waves of actions: bundle measures to survey and control cross transmission of MRSA and extended-spectrum betalactamase producing enterobacteria (ESBL) in 1993, large campaign to promote the use of alcohol-based hand rub solution (ABHRS) in 2001, specific strategy to quickly control the spread of emerging MDR (vancomycin resistant Enterococcus, VRE; carbapenemase producing enterobacteria, CPE) in 2006, large campaign to decrease antibiotics consumption in 2006.
Following this programme, the ABHRS consumption dramatically increased, the antibiotic consumption decreased by 10%, the incidence of MRSA, including MRSA bacteraemia, decreased by 2/3, all VRE and CPE events were rapidly controlled. However, the incidence of ESBL, mainly Klebsiella pneumoniae and Escherichia coli, that remained low and stable until 2003 increased markedly afterwards, justifying adapting our programme in the future.
Conclusion
A sustained and coordinated strategy can lead to control multidrug resistant bacteria at the level of a large multihospital institution.
doi:10.1186/2047-2994-1-9
PMCID: PMC3436665  PMID: 22958336
antibiotic resistance control; carbapenemase producing enterobacteria; CPE; vancomycin resistant enterococci; VRE; MRSA; quality programme; healthcare associated infections; HAI
15.  Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study 
Critical Care  2011;15(4):R171.
Introduction
Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question.
Methods
We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug.
Results
Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 [6-14] vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug.
Conclusions
Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution.
doi:10.1186/cc10317
PMCID: PMC3387613  PMID: 21767409
statin; discontinuation; blood concentration; sepsis
16.  Preventing ventilator associated pneumonia 
BMJ : British Medical Journal  2007;334(7599):861-862.
Oral antiseptic agents should be part of a multifaceted preventive care package
doi:10.1136/bmj.39185.380405.BE
PMCID: PMC1857768  PMID: 17463422
17.  Risk stratification of early admission to the intensive care unit of patients with no major criteria of severe community-acquired pneumonia: development of an international prediction rule 
Critical Care  2009;13(2):R54.
Introduction
To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3.
Methods
Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support).
Results
A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population.
Conclusions
The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions.
doi:10.1186/cc7781
PMCID: PMC2689501  PMID: 19358736
18.  Brachyspira pilosicoli bloodstream infections: Case report and review of the literature 
Brachyspira pilosicoli is the etiologic agent of human and animal intestinal spirochetosis and is rarely implicated as a cause of bacteremia. Here, we describe the case of a B. pilosicoli spirochetemia in a 53-year-old male patient suffering from cardiogenic shock. This fastidious bacterium was isolated from blood, likely after translocation from the intestinal tract. Blood cultures were positive after 5 days of incubation (one day after the patient's death), highlighting the problem of the recovery of such type of fastidious bacterium. Identification was achieved by molecular methods (16S rRNA sequencing). A review of the English literature found only 8 cases of bacteremia caused by B. pilosicoli, mostly in immunocompromised or critically ill patients. Finally, difficulties in rapid and accurate diagnosis of B. pilosicoli bloodstream infections, in vitro antimicrobial susceptibility of human clinical isolates, and therapeutic options are discussed.
doi:10.1186/1476-0711-7-19
PMCID: PMC2561035  PMID: 18817558
19.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 
Intensive Care Medicine  2007;34(1):17-60.
Objective
To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004.
Design
Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding.
Methods
We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations.
Results
Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D).
Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B).
Conclusion
There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
doi:10.1007/s00134-007-0934-2
PMCID: PMC2249616  PMID: 18058085
Sepsis; Severe sepsis; Septic shock; Sepsis syndrome; Infection; GRADE; Guidelines; Evidence-based medicine; Surviving Sepsis Campaign; Sepsis bundles
20.  Ethics roundtable debate: A patient dies from an ICU-acquired infection related to methicillin-resistant Staphylococcus aureus – how do you defend your case and your team? 
Critical Care  2004;9(1):5-9.
An elderly patient dies from septic shock in the intensive care unit. This is perhaps not an unusual scenario, but in this case the sepsis happens to have been due to methicillin-resistant Staphylococcus aureus, possibly related to a catheter, and possibly transmitted from a patient in a neighbouring room by less than adequate compliance with infection control procedures. The family decides to sue. We present how experts from four different countries assess the medicolegal issues involved in this case.
doi:10.1186/cc3016
PMCID: PMC1065110  PMID: 15693971
infection control procedures; medicolegal; MRSA; transmission
21.  Usefulness of Routine Epicardial Pacing Wire Culture for Early Prediction of Poststernotomy Mediastinitis 
Journal of Clinical Microbiology  2004;42(11):5245-5248.
Poststernotomy mediastinitis (PSM) is one of the most serious complications of cardiac surgery, and its associated morbidity and mortality demand early recognition for emergency therapy. In this study, we investigated the usefulness of epicardial pacing wire (EPW) cultures for the prediction of PSM. Among 2,200 patients who underwent a cardiac surgical procedure at our hospital between 1 January 1999 and 31 December 2001, 82 (3.7%) had PSM; Staphylococcus aureus was the organism (45.1%) most frequently isolated at the time of surgical debridement. EPWs from 1,607 (73.0%) patients, 73 (4.5%) of whom developed PSM, were cultured. EPW cultures from 466 (29.0%) were positive, most often (74.9%) for coagulase-negative Staphylococci. EPW cultures were truly positive in 26 cases, truly negative in 1,106 cases, falsely positive in 428 cases, and falsely negative in 47 cases (with sterile cultures in 35 cases and a culture positive for an organism different from that isolated at the time of debridement in 12 cases). EPW culture had a positive predictive value of only 5.7% and a high negative predictive value (95.9%) for the diagnosis of PSM, with an accuracy of 70.4%. However, the likelihood ratio of positive (1.27) and negative (0.89) tests indicated only small changes in pretest-to-posttest probability. Therefore, a strategy of routine culture of EPWs to predict PSM seems questionable.
doi:10.1128/JCM.42.11.5245-5248.2004
PMCID: PMC525282  PMID: 15528721
22.  Outpatient Antibiotic Use and Prevalence of Antibiotic-Resistant Pneumococci in France and Germany: A Sociocultural Perspective 
Emerging Infectious Diseases  2002;8(12):1460-1467.
The prevalence of penicillin-nonsusceptible pneumococci is sharply divided between France (43%) and Germany (7%). These differences may be explained on different levels: antibiotic- prescribing practices for respiratory tract infections; patient-demand factors and health-belief differences; social determinants, including differing child-care practices; and differences in regulatory practices. Understanding these determinants is crucial for the success of possible interventions. Finally, we emphasize the overarching importance of a sociocultural approach to preventing antibiotic resistance in the community.
doi:10.3201/eid0812.010533
PMCID: PMC2738507  PMID: 12498664
Antibiotics; therapeutic use; culture; drug resistance; France; Germany; physician’s practice patterns; epidemiology; Streptococcus pneumoniae
23.  Efficacy of handrubbing with alcohol based solution versus standard handwashing with antiseptic soap: randomised clinical trial 
BMJ : British Medical Journal  2002;325(7360):362.
Objective
To compare the efficacy of handrubbing with an alcohol based solution versus conventional handwashing with antiseptic soap in reducing hand contamination during routine patient care.
Design
Randomised controlled trial during daily nursing sessions of 2 to 3 hours.
Setting
Three intensive care units in a French university hospital.
Participants
23 healthcare workers.
Interventions
Handrubbing with alcohol based solution (n=12) or handwashing with antiseptic soap (n=11) when hand hygiene was indicated before and after patient care. Imprints taken of fingertips and palm of dominant hand before and after hand hygiene procedure. Bacterial counts quantified blindly.
Main outcome measures
Bacterial reduction of hand contamination.
Results
With handrubbing the median percentage reduction in bacterial contamination was significantly higher than with handwashing (83% v 58%, P=0.012), with a median difference in the percentage reduction of 26% (95% confidence interval 8% to 44%). The median duration of hand hygiene was 30 seconds in each group.
Conclusions
During routine patient care handrubbing with an alcohol based solution is significantly more efficient in reducing hand contamination than handwashing with antiseptic soap.
What is already known on this topicTo improve compliance with hand hygiene during patient care, handrubbing with an alcohol based solution has been proposed as a substitute for handwashing because of its rapid action and accessibilityExperimental studies show that handrubbing is at least as effective as medicated soap in reducing artificial contamination of handsMany healthcare workers still have reservations regarding its efficacy and are reluctant to use this techniqueWhat this study addsWhen used in routine practice, handrubbing with an alcohol based solution after contact with patients achieved a greater reduction in bacterial contamination of hands than conventional handwashing with medicated soap
PMCID: PMC117885  PMID: 12183307

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