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1.  Complete Genome Sequences of Nitrofurantoin-Sensitive and -Resistant Escherichia coli ST540 and ST2747 Strains 
Genome Announcements  2014;2(2):e00239-14.
Widespread multidrug resistance in Escherichia coli has necessitated the reintroduction of older antibiotics, such as nitrofurantoin. However, mechanisms by which resistance to nitrofurantoin emerges in E. coli are not well elucidated. Toward this aim, we sequenced two nitrofurantoin-sensitive E. coli sequence types (ST540 and ST2747) and their four nitrofurantoin-resistant derivatives generated in vitro under aerobic and anaerobic growth conditions.
PMCID: PMC3983296  PMID: 24723707
2.  Multilevel competing risk models to evaluate the risk of nosocomial infection 
Critical Care  2014;18(2):R64.
Risk factor analyses for nosocomial infections (NIs) are complex. First, due to competing events for NI, the association between risk factors of NI as measured using hazard rates may not coincide with the association using cumulative probability (risk). Second, patients from the same intensive care unit (ICU) who share the same environmental exposure are likely to be more similar with regard to risk factors predisposing to a NI than patients from different ICUs. We aimed to develop an analytical approach to account for both features and to use it to evaluate associations between patient- and ICU-level characteristics with both rates of NI and competing risks and with the cumulative probability of infection.
We considered a multicenter database of 159 intensive care units containing 109,216 admissions (813,739 admission-days) from the Spanish HELICS-ENVIN ICU network. We analyzed the data using two models: an etiologic model (rate based) and a predictive model (risk based). In both models, random effects (shared frailties) were introduced to assess heterogeneity. Death and discharge without NI are treated as competing events for NI.
There was a large heterogeneity across ICUs in NI hazard rates, which remained after accounting for multilevel risk factors, meaning that there are remaining unobserved ICU-specific factors that influence NI occurrence. Heterogeneity across ICUs in terms of cumulative probability of NI was even more pronounced. Several risk factors had markedly different associations in the rate-based and risk-based models. For some, the associations differed in magnitude. For example, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with modest increases in the rate of nosocomial bacteremia, but large increases in the risk. Others differed in sign, for example respiratory vs cardiovascular diagnostic categories were associated with a reduced rate of nosocomial bacteremia, but an increased risk.
A combination of competing risks and multilevel models is required to understand direct and indirect risk factors for NI and distinguish patient-level from ICU-level factors.
PMCID: PMC4056071  PMID: 24713511
3.  Epidemiological Interpretation of Studies Examining the Effect of Antibiotic Usage on Resistance 
Clinical Microbiology Reviews  2013;26(2):289-307.
Bacterial resistance to antibiotics is a growing clinical problem and public health threat. Antibiotic use is a known risk factor for the emergence of antibiotic resistance, but demonstrating the causal link between antibiotic use and resistance is challenging. This review describes different study designs for assessing the association between antibiotic use and resistance and discusses strengths and limitations of each. Approaches to measuring antibiotic use and antibiotic resistance are presented. Important methodological issues such as confounding, establishing temporality, and control group selection are examined.
PMCID: PMC3623381  PMID: 23554418
4.  Infection control interventions in small rural hospitals with limited resources: results of a cluster-randomized feasibility trial 
There are few reports on the feasibility of conducting successful infection control (IC) interventions in rural community hospitals.
Ten small rural community hospitals in Idaho and Utah were recruited to participate in a cluster-randomized trial of multidimensional IC interventions to determine their feasibility in the setting of limited resources. Five hospitals were randomized to develop individualized campaigns to promote HH, isolation compliance, and outbreak control. Five hospitals were randomized to continue with current IC practices. Regular blinded observations of hand hygiene (HH) compliance were conducted in all hospitals as the primary outcome measure. Additionally, periodic prevalence studies of patient colonization with resistant pathogens were performed. The 5-months intervention time period was compared to a 4-months baseline period, using a multi-level logistic regression model.
The intervention hospitals implemented a variety of strategies. The estimated average absolute change in “complete HH compliance” in intervention hospitals was 20.1% (range, 7.8% to 35.5%) compared to −3.1% (range −6.3% to 5.9%) in control hospitals (p = 0.001). There was an estimated average absolute change in “any HH compliance” of 28.4% (range 17.8% to 38.2%) in intervention hospitals compared to 0.7% (range −16.7 to 20.7%) in control hospitals (p = 0.010). Active surveillance culturing demonstrated an overall prevalence of MRSA carriage of 9.7%.
A replicable intervention significantly improved hand hygiene as a primary outcome measure despite barriers of geographic distance and lack of experience with study protocols. Active surveillance culturing identified unsuspected reservoirs of MRSA colonization and further promoted IC activity.
PMCID: PMC3986470  PMID: 24678604
Hand hygiene; Epidemiology; United States; Transmission; Clinical trial; MRSA
5.  Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study 
Critical Care  2014;18(2):R42.
Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome.
In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality.
Median time to AT was 2.1 (IQR 0.8 – 6.0) hours and 3 hours (-0.1 – 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001).
A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.
PMCID: PMC4057316  PMID: 24589043
6.  Year in review 2011: Critical Care - infection 
Critical Care  2012;16(6):242.
There is an ever-growing importance for critical assessment of benefits and harms of various strategies with regards to antibiotic stewardship, infection control, molecular detection of pathogens and adequate treatment of multidrug-resistant organisms in ICUs. Ongoing financial constraints globally, changing demographics with an increasing and aging population and the slow introduction of new antibiotics make the utilisation of the best available evidence and goal-directed strategies essential in the ICU setting. This review will summarise findings from some of the recent major publications in the area of infectious diseases with emphasis on the role of behaviour change strategies for infection control purposes, the role of biomarkers such as C-reactive protein and procalcitonin, and the impact of molecular diagnostics in clinical decision-making. Furthermore, we will update readers on some recent findings in relation to invasive fungal infections, community-acquired pneumonia and ventilator-associated pneumonia in ICU patients.
PMCID: PMC3672546
7.  Epidemiology of Methicillin-Resistant Staphylococcus aureus Carriage and MRSA Surgical Site Infections in Patients Undergoing Colorectal Surgery: A Cohort Study in Two Centers 
Surgical Infections  2012;13(6):401-405.
Surgical site infections (SSIs) after colorectal surgery usually are caused by commensal intestinal bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) may be responsible for additional SSI-related morbidity. The aim of this retrospective cohort study was to describe the epidemiology of SSIs caused by MRSA after colorectal surgery in two tertiary-care centers, one in Geneva, Switzerland (G), and the other in Chicago, Illinois (C).
Adult patients undergoing colorectal resections during periods of universal screening for MRSA on admission were identified retrospectively. Demographic characteristics, surgery-related factors, and occurrence of MRSA SSI were compared in patients with and without MRSA carriage before surgery.
There were 1,069 patients (G=194, C=875) with a median age of 67 years fulfilling the inclusion criteria. Of these, 45 patients (4.2%) had a positive MRSA screening result within 30 days before surgery (G=18, C=27; p<0.001). Ten patients (0.9%; G=6, C=4) developed MRSA SSI, detected a median of 17.5 days after surgery, but only two of them were MRSA-positive before surgery. Nine of the 45 MRSA carriers identified by screening received pre-operative prophylaxis with vancomycin (G 6/18, C 3/27), and 17 of these patients (37.8%; G 7/18, C 10/27) were started on MRSA decolonization therapy before surgery. Pre-operative administration of either decolonization or vancomycin was not protective against MRSA SSI (p=0.49).
Methicillin-resistant S. aureus seems to be an infrequent cause of SSI after colorectal resections, even in MRSA carriers. Systematic universal screening for MRSA carriage prior to colorectal surgery may not be beneficial for the individual patient. Post-operative factors seem to be important in MRSA infections, as the majority of MRSA SSIs occurred in patients negative for MRSA carriage.
PMCID: PMC3532004  PMID: 23240722
8.  Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum 
Antimicrobial resistance (AMR) is now a global threat. Its emergence rests on antimicrobial overuse in humans and food-producing animals; globalization and suboptimal infection control facilitate its spread. While aggressive measures in some countries have led to the containment of some resistant gram-positive organisms, extensively resistant gram-negative organisms such as carbapenem-resistant enterobacteriaceae and pan-resistant Acinetobacter spp. continue their rapid spread. Antimicrobial conservation/stewardship programs have seen some measure of success in reducing antimicrobial overuse in humans, but their reach is limited to acute-care settings in high-income countries. Outside the European Union, there is scant or no oversight of antimicrobial administration to food-producing animals, while evidence mounts that this administration leads directly to resistant human infections. Both horizontal and vertical infection control measures can interrupt transmission among humans, but many of these are costly and essentially limited to high-income countries as well. Novel antimicrobials are urgently needed; in recent decades pharmaceutical companies have largely abandoned antimicrobial discovery and development given their high costs and low yield. Against this backdrop, international and cross-disciplinary collaboration appears to be taking root in earnest, although specific strategies still need defining. Educational programs targeting both antimicrobial prescribers and consumers must be further developed and supported. The general public must continue to be made aware of the current scale of AMR’s threat, and must perceive antimicrobials as they are: a non-renewable and endangered resource.
PMCID: PMC4131211  PMID: 24237856
Antimicrobial resistance; Antimicrobial conservation; Antibiotic stewardship; Infection control; Hand hygiene; Surveillance networks; Care bundles; Environment; Regulations; Human medicine; Animal medicine; Global health; World Healthcare-Associated Infections Forum
9.  Comparison of strategies to reduce meticillin-resistant Staphylococcus aureus rates in surgical patients: a controlled multicentre intervention trial 
BMJ Open  2013;3(9):e003126.
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.
Prospective, controlled, interventional cohort study, with 6-month baseline, 12-month intervention and 6-month washout phases.
33 surgical wards of 10 hospitals in nine countries in Europe and Israel.
All patients admitted to the enrolled wards for more than 24 h.
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.
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).
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 identifier: NCT00685867
PMCID: PMC3780302  PMID: 24056477
Infection Control < Infectious Diseases; Surgery
10.  Carriage of extended-spectrum beta-lactamase-producing enterobacteriacae among internal medicine patients in Switzerland 
The incidence of extended-spectrum beta-lactamase producing-enterobacteriacae (ESBL-E) infection is rising worldwide. We aimed to determine the prevalence and nosocomial acquisition rate of ESBL-E as well as the risk factors for ESBL-E carriage and acquisition amongst patients consecutively admitted to 13 internal medicine units at our hospital who were not previously known to be ESBL-E carriers.
We screened all patients admitted or transferred to internal medicine units for ESBL-E on admission and discharge using rectal swabs. Of 1072 patients screened, 51 (4.8%) were carriers of an ESBL-E at admission. Of 473 patients who underwent admission and discharge screening, 21 (4.4%) acquired an ESBL-E. On multivariate analysis, diabetes mellitus without end-organ complications (OR 2.87 [1.09-7.08]), connective tissue disease (OR 7.22 [1.17-44.59]), and liver failure (OR 8.39 [1.55-45.45]) were independent risk factors for carriage of an ESBL-E upon admission to hospital (area under the ROC curve, 0.68). Receipt of a first- or second-generation cephalosporin (OR 9.25 [2.22-37.82]), intra-hospital transfer (OR 6.68 [1.71-26.06]), and a hospital stay >21 days (OR 25.17 [4.18-151.68]) were associated with acquisition of an ESBL-E during hospitalisation; whilst admission from home was protective (OR 0.16 [0.06-0.39]) on univariate regression. No risk profile with sufficient accuracy to predict previously unknown carriage on admission or acquisition of ESBL-E could be developed using readily available patient information.
ESBL-E carriage is endemic amongst internal medicine patients at our institution. We were unable to develop a clinical risk profile to accurately predict ESBL-E carriage amongst these patients.
PMCID: PMC3711782  PMID: 23759067
Extended-spectrum beta-lactamase producing enterobacteraciae; Infection control; Antimicrobial resistance
11.  Methicillin-resistant Staphylococcus aureus risk profiling: who are we missing? 
Targeted screening of patients at high risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage is an important component of MRSA control programs, which rely on prediction tools to identify those high-risk patients. Most previous risk studies reported a substantial rate of patients who are eligible for screening, but failed to be enrolled. The characteristics of these missed patients are seldom described. We aimed to determine the rate and characteristics of patients who were missed by a MRSA screening programme at our institution to see how the failure to include these patients might impact the accuracy of clinical prediction tools.
From March-June 2010 all patients admitted to 13 internal medicine wards at the University of Geneva Hospital (HUG) were prospectively screened for MRSA carriage. Of 1968 patients admitted to the ward, 267 patients (13.6%) failed to undergo appropriate MRSA screening. Forty-one (2.4%) screened patients were MRSA carriers at admission. On multivariate regression, patients who were missed by screening were more likely to be aged < 50 years (OR 2.4 [1.4-3.9]), transferred to internal medicine from another ward in the hospital (OR 2.8 [1.1-7.1]), and have a history of malignancy (OR 3.2[2.1-5.1]). There was no significant difference in the rate of previous MRSA carriage between screened and unscreened patients.
Our findings highlight the potential bias that “missed” patients may introduce into MRSA risk scores. Reporting on the proportions and characteristics of missed patients is essential for accurate interpretation of MRSA prediction tools.
PMCID: PMC3672049  PMID: 23721630
Carrier state; Epidemiology; MRSA; Prevalence; Probability; Predictive value of tests; Staphylococcal infection; Switzerland
12.  Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier? 
Critical Care  2012;16(3):222.
Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection.
PMCID: PMC3580598  PMID: 22647543
13.  Correction: Assisted Knowledge Discovery for the Maintenance of Clinical Guidelines 
PLoS ONE  2013;8(5):10.1371/annotation/b38c6896-f340-45cb-a9ca-ceff49330c3f.
PMCID: PMC3651234
14.  Epidemiology and acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in a septic orthopedic ward 
SpringerPlus  2013;2:91.
Wards cohorting infected orthopaedic patients may be particularly prone to transmitting extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). We analyze their epidemic pattern by performing molecular typing of ESBL-E isolated from patients and healthcare workers (HCW) from our septic ward. Between March 2010 and November 2011, 186 patients were admitted. Among 565 anal swabs, ESBL-E were detected in 204 samples from 45 patients, suggesting prolonged carriage in affected patients. Among 25 cases with identical ESBL-E species and positive epidemiological links, only 9 were really attributable to our service. We also screened 41 healthcare workers (HCW) on 49 occasions during the study period. Six samples (13%) were positive. None of the ESBL-E detected in HCW were related to any of the patient isolates. Among 60 environmental samples taken at the peak of the epidemic none revealed ESBL-E. We conclude that HCW also were anal carriers of ESBL-E, however the ESBL- strains from the HCW were not the same strains isolated from patients in the septic ward. Moreover, the epidemiological attribution of ESBL by simple vicinity, timing, and species identification might grossly overestimate transmission within a given unit.
PMCID: PMC3604582  PMID: 23539506
ESBL; Septic orthopedics; Patients; Healthcare workers; Antibiotics
15.  Is patient isolation the single most important measure to prevent the spread of multidrug-resistant pathogens? 
Virulence  2013;4(2):163-171.
Isolation or cohorting of infected patients is an old concept. Its purpose is to prevent the transmission of microorganisms from infected or colonized patients to other patients, hospital visitors, and health care workers, who may subsequently transmit them to other patients or become infected or colonized themselves. Because the process of isolating patients is expensive, time-consuming, often uncomfortable for patients and may impede care, it should be implemented only when necessary. Conversely, failure to isolate a patient with multidrug-resistant microorganisms may lead to adverse outcomes, and may ultimately be expensive when one considers the direct costs of an outbreak investigation and the indirect costs of lost productivity. In this review, we argue that contact precautions are essential to control the spread of epidemic and endemic multidrug-resistant microorganisms, and discuss limitations of some available data.
PMCID: PMC3654617  PMID: 23302791
isolation; active surveillance; infection control; multidrug-resistant pathogens
16.  Year in review 2010: Critical Care - infection 
Critical Care  2011;15(6):238.
Infections remain among the most important concerns in critically ill patients. Early and reliable diagnosis of infection still poses difficulties in this setting but also represents a crucial step toward appropriate antimicrobial therapy. Increasing antimicrobial resistance challenges established approaches to the optimal management of infections in the intensive care unit. Rapid infection diagnosis, antibiotic dosing and optimization through pharmacologic indices, progress in the implementation of effective antimicrobial stewardship and infection control programs, and management of fungal infections are some of the most relevant issues in this special patient population. During the last 18 months, Critical Care and other journals have provided a wide array of descriptive and interventional clinical studies and scientific reports helping clinical investigators and critical care physicians to improve diagnosis, management, and therapy of infections in critically ill patients.
PMCID: PMC3388701  PMID: 22152031
17.  High Prevalence of Isolates with Reduced Glycopeptide Susceptibility in Persistent or Recurrent Bloodstream Infections Due to Methicillin-Resistant Staphylococcus aureus 
Reduced susceptibility to glycopeptides in methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates is considered a risk factor for failure of glycopeptide therapy. We compared the prevalences of MRSA isolates with reduced glycopeptide susceptibility in patients with versus without persistent or recurrent MRSA bloodstream infections. A retrospective cohort study at the University Hospital of Geneva identified 27 patients with persistent or recurrent clonally related MRSA bacteremic episodes over an 8-year period, which included 208 consecutive nosocomial MRSA bacteremic episodes. Vancomycin and teicoplanin MICs were determined by a modified macrodilution assay allowing improved detection of glycopeptide-intermediate MRSA isolates (GISA), characterized by elevated teicoplanin or/and vancomycin MICs (≥4 μg/ml). For 16 patients (59%), their pretherapy and/or posttherapy MRSA isolates showed elevated teicoplanin MICs, among which 10 (37%) concomitantly displayed elevated vancomycin MICs. In contrast, 11 other patients (41%) were persistently or recurrently infected with non-GISA isolates. In comparison, only 39 (22%) of 181 single isolates from patients with no microbiological evidence of persistent or recurrent infections showed elevated teicoplanin MICs, among which 14 (8%) concomitantly displayed elevated vancomycin MICs. Clinical, microbiological, and pharmacokinetic variables for patients persistently or recurrently infected with GISA or non-GISA isolates were similar. Bacteremic patients with a poor response to glycopeptide therapy had a 2.8-fold- and 4.8-fold-higher rates of MRSA isolates displaying elevated teicoplanin and vancomycin MICs, respectively, than patients with single isolates (P < 0.0001). Detection of elevated teicoplanin MICs may help to predict a poor response to glycopeptide therapy in MRSA bacteremic patients.
PMCID: PMC3294919  PMID: 22155824
19.  Molecular and Epidemiological Evaluation of Strain Replacement in Patients Previously Harboring Gentamicin-Resistant MRSA ▿ †  
Journal of Clinical Microbiology  2011;49(11):3880-3884.
Gentamicin-susceptible methicillin-resistant Staphylococcus aureus (GS-MRSA) clones have gradually replaced gentamicin-resistant MRSA (GR-MRSA) clones in many European countries. We studied molecular and epidemiological aspects of MRSA strain replacement in individual patients. All patients from whom at least 2 MRSA strains showing different gentamicin susceptibility patterns were isolated between 1996 and 2008 were retrospectively identified. Staphylococcal cassette chromosome mec (SCCmec) type and clonality between isolates were determined using molecular methods. Risk factors for individual GR-MRSA SCCmec I (prevalent clone) strain replacement with GS-MRSA non-SCCmec I types were studied in a nested case-crossover study (n = 55 patients). MRSA strain replacement was observed in 127 patients, 85 (67%) of whom were initially colonized with GR-MRSA replaced subsequently by GS-MRSA. Most GS-MRSA replacement strains (50; 59%) possessed SCCmec IV. All MRSA isolate pairs from the same patient that consisted of different gentamicin susceptibility and SCCmec types were also genotypically different. Exposure to domiciliary nursing assistance (odds ratio [OR], 8.1; 95% confidence interval [CI], 1.2 to 53.7) and high Charlson scores (OR, 7.1; 95% CI, 1.1 to 46.8) were associated with individual strain replacement. In individual patients, exogenous acquisition of a different MRSA strain was responsible for strain replacement in most cases. Domiciliary nursing assistance could be a target for specific control measures to prevent transmission of GS-MRSA in our setting.
PMCID: PMC3209128  PMID: 21918027
20.  Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action 
Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs.
PMCID: PMC3436635  PMID: 22958833
antibiotic resistance; antibiotic stewardship; infection control; hand hygiene; surveillance networks; care bundles; environment; regulations; human medicine; animal medicine
21.  Clostridium: Transmission difficile? 
PLoS Medicine  2012;9(2):e1001171.
Stephan Harbarth and Matthew Samore discuss the implications, and the limitations, of new research that might indicate that most Clostridium difficile cases are imported into hospitals.
PMCID: PMC3274498  PMID: 22346737
22.  “Ten Commandments” for the Appropriate use of Antibiotics by the Practicing Physician in an Outpatient Setting 
A multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients’ compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically – but intelligently; know local susceptibility trends, and also surveillance limitations.
PMCID: PMC3225075  PMID: 22164154
antibiotic stewardship; antibiotic resistance; guidelines; generic antibiotics; self-prescription; treatment compliance
23.  Year in review 2009: Critical Care - infection 
Critical Care  2010;14(6):240.
In 2009 Critical Care provided important and clinically relevant research data for management and prevention of infections in critically ill patients. The present review summarises the results of these observational studies and clinical trials and discusses them in the context of the current relevant scientific and clinical background. In particular, we discuss recent epidemiologic data on nosocomial infections in intensive care units, present new approaches to prevention of ventilator-associated pneumonia, describe recent advances in biomarker-guided antibiotic stewardship and attempt to briefly summarise specific challenges related to the management of infections caused by multidrug-resistant microorganisms and influenza A (H1N1).
PMCID: PMC3220050  PMID: 21122168
24.  Impact of Outpatient Antibiotic Use on Carriage of Ampicillin-Resistant Escherichia coli▿  
Studies about the relationship between antibiotic consumption and carriage of antibiotic-resistant Escherichia coli in individual patients have yielded conflicting results. The goal of this study was to identify individual- and household-level factors associated with carriage of ampicillin (AMP)-resistant E. coli during consumption of a course of oral antibiotics. We enrolled outpatients and their families in a prospective household study of AMP-resistant or AMP-susceptible E. coli carriage. Two kinds of index patients were identified. Group 1 consisted of outpatients who were being initiated on a new antibiotic course at the time of a clinic visit, and group 2 consisted of outpatients not starting antibiotics. Each participant was asked to submit three stool swab samples (at baseline, week 1, and week 4) and to complete a questionnaire. Antimicrobial susceptibility testing was performed on each phenotypically distinct E. coli colony. The study included 149 group 1 households (total, 570 participants) and 38 group 2 households (total, 131 participants). AMP-resistant E. coli was recovered from 29% of stool samples. Observed associations with antibiotic exposure varied by drug class. Penicillins, which were the most frequently prescribed drug class, were associated with a modest increase in AMP-resistant E. coli carriage and a modest decrease in AMP-susceptible E. coli carriage. Neither change by itself was statistically significant. Macrolides were associated with reduced carriage of both AMP-resistant E. coli and AMP-susceptible E. coli (P < 0.05). Both AMP-resistant and AMP-susceptible E. coli demonstrated household clustering (P < 0.001). In summary, the overall effect of antibiotics on individual risk of carriage of AMP-resistant E. coli was small. However, even a modest alteration of the competitive balance between AMP-resistant and AMP-susceptible E. coli may promote population spread of resistant E. coli. Examining changes in both resistant and susceptible organisms in antibiotic-treated individuals and their close contacts improves understanding of antibiotic selection pressure.
PMCID: PMC3067088  PMID: 21115789
25.  Think (Gram) negative! 
Critical Care  2010;14(3):171.
The increasing prevalence of multiresistant Gram-negative bacteria of the Enterobacteriaceae family in Europe is a worrisome phenomenon. Extended spectrum betalactamase-producing Escherichia coli strains are widespread in the community and are frequently imported into the hospital. Of even more concern is the spread of carbapenem-resistant strains of Klebsiella spp. from regions where they are already endemic. Antibiotic use is a main driver of antibiotic resistance, which again increases broad spectrum antibiotic use, resulting in a vicious circle that is difficult to interrupt. The present commentary highlights important findings of a surveillance study of antimicrobial use and resistance in German ICUs over 8 years with a focus on Gram-negative resistance.
PMCID: PMC2911742  PMID: 20587087

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