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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.  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
3.  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  PMID: 23256824
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  Herpes Zoster Vaccine Effectiveness against Incident Herpes Zoster and Post-herpetic Neuralgia in an Older US Population: A Cohort Study 
PLoS Medicine  2013;10(4):e1001420.
Sinead Marie Langan and colleagues studied a cohort of more than 750,000 individuals over the age of 65 years to assess whether herpes zoster vaccine is effective against incident zoster and post-herpetic neuralgia in an older population.
Herpes zoster is common and has serious consequences, notably post-herpetic neuralgia (PHN). Vaccine efficacy against incident zoster and PHN has been demonstrated in clinical trials, but effectiveness has not been studied in unselected general populations unrestricted by region, full health insurance coverage, or immune status. Our objective was to assess zoster vaccine effectiveness (VE) against incident zoster and PHN in a general population-based setting.
Methods and Findings
A cohort study of 766,330 fully eligible individuals aged ≥65 years was undertaken in a 5% random sample of Medicare who received and did not receive zoster vaccination between 1st January 2007 and 31st December 2009.
Incidence rates and hazard ratios for zoster and PHN were determined in vaccinated and unvaccinated individuals. Analyses were adjusted for age, gender, race, low income, immunosuppression, and important comorbidities associated with zoster, and then stratified by immunosuppression status. Adjusted hazard ratios were estimated using time-updated Cox proportional hazards models.
Vaccine uptake was low (3.9%) particularly among black people (0.3%) and those with evidence of low income (0.6%). 13,112 US Medicare beneficiaries developed incident zoster; the overall zoster incidence rate was 10.0 (9.8–10.2) per 1,000 person-years in the unvaccinated group and 5.4 (95% CI 4.6–6.4) per 1,000 person-years in vaccinees, giving an adjusted VE against incident zoster of 0.48 (95% CI 0.39–0.56). In immunosuppressed individuals, VE against zoster was 0.37 (95% CI 0.06–0.58). VE against PHN was 0.59 (95% CI 0.21–0.79).
Vaccine uptake was low with variation in specific patient groups. In a general population cohort of older individuals, zoster vaccination was associated with reduction in incident zoster, including among those with immunosuppression. Importantly, this study demonstrates that zoster vaccination is associated with a reduction in PHN.
Please see later in the article for the Editors' Summary
Editors' Summary
Chickenpox is an extremely common childhood infectious disease that is caused by the herpes varicella-zoster virus. Children usually recover quickly from chickenpox, but dormant varicella-zoster virus persists throughout life inside the nervous system. The dormant virus causes no symptoms but if it becomes reactivated, it causes shingles (zoster), a painful skin rash. Anyone who has had chickenpox can develop shingles but shingles is most common and most severe in 60–80-year-old people. Indeed, about half of people who live to 85 will have an episode of shingles. Early signs of shingles include burning or shooting pain and tingling or itching. Blister-like sores, which last from 1–14 days, then develop in a region of one side of the body or on one side of the face. The pain of shingles can be debilitating and can continue after the rash disappears—“post-herpetic neuralgia,” which can last for months to years, greatly reduces the quality of life. There is no cure for shingles but early treatment with antivirals may help to prevent lingering pain by inhibiting viral replication.
Why Was This Study Done?
Shingles vaccination can prevent shingles or lessen its effects. In clinical trials, vaccination reduced the incidence of shingles (the proportion of a population who develop shingles in a year) and the incidence of post-herpetic neuralgia, and vaccination against shingles is now recommended in the US for everyone over the age of 60 except individuals with a weakened immune system (for example, people with HIV/AIDS). However, these clinical trials determined the vaccine's efficacy in selected populations under controlled conditions. How effective is the vaccine in unselected populations in routine clinical use? In this cohort study, the researchers assess zoster (shingles) vaccine effectiveness against incident shingles and post-herpetic neuralgia in an unselected population of older individuals in the US. A cohort study follows a group of individuals who differ with respect to specific factors (in this study, vaccination against shingles) to determine how these factors affect the rates of specific outcomes (shingles and post-herpetic neuralgia).
What Did the Researchers Do and Find?
The researchers undertook their cohort study in 766,330 randomly chosen Medicare beneficiaries aged 65 years or more. Medicare is a US government health insurance scheme that mainly helps to pay the health care costs of people aged 65 or older. The researchers used Medicare administrative data to identify which cohort members received zoster vaccination between January 2007 and December 2009 and which developed incident shingles (defined as a first diagnosis of shingles combined with the use of antivirals) or post-herpetic neuralgia (defined as a code for post-herpetic neuralgia, non-specific neuralgia, or a second diagnostic code for shingles 90 days after the first diagnosis combined with a prescription for pain relief, an anticonvulsant, or an antidepressant). Vaccine uptake was low in this unselected study population—only 3.9% of the participants were vaccinated. The vaccination rate was particularly low among black people (0.6% of person-time) and among people with a low income (0.3%). About 13,000 participants developed incident shingles. The shingles incidence rate was 10.0 per 1,000 person-years among unvaccinated participants and 5.4 per 1,000 person-years among vaccinated participants. Vaccine effectiveness against incident shingles was 48%. That is, vaccination reduced the incidence of shingles by 48% (in other words, approximately half as many vaccinated individuals developed shingles as those who were not vaccinated). Vaccine effectiveness against incident shingles among immunosuppressed individuals was lower (37%). Finally, vaccine effectiveness against post-herpetic neuralgia was 59%.
What Do These Findings Mean?
These findings show that shingles vaccine uptake is low among elderly people in the US and varies between different patient groups. They show that shingles vaccination is effective against incident shingles in a general population of older individuals, including those who are immunosuppressed, and suggest that shingles vaccination is effective against post-herpetic neuralgia. However, because these findings rely on administrative data, their accuracy may be affected by misclassification of vaccination and of outcomes. Moreover, because shingles vaccination was not randomized, the vaccinated individuals might have shared other characteristics that were actually responsible for their lower incidence of shingles and/or post-herpetic neuralgia compared to unvaccinated individuals. Despite these limitations, these findings provide useful information for policy makers in countries that are currently considering the introduction of shingles vaccination into routine practice. Moreover, they highlight the need to increase shingles vaccination among elderly individuals in the US, the section of the population at the highest risk of post-herpetic neuralgia.
Additional Information
Please access these Web sites via the online version of this summary at 10.1371/journal.pmed.1001420.
The US Centers for Disease Control and Prevention have detailed information about all aspects of shingles (zoster), including information on vaccination for the public and for health care professionals, and a personal story about shingles
The NIH Senior Health website includes information on shingles and a video describing a personal experience of shingles
The UK National Health Service Choices also provides information about all aspects of shingles and a personal story
MedlinePlus provides links to other resources about shingles (in English and Spanish)
The British Association of Dermatologists website has an information leaflet on shingles
The New Zealand Dermatological Society website has a leaflet on shingles
PMCID: PMC3621740  PMID: 23585738
11.  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
12.  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
13.  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
14.  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
15.  Reduction in Clostridium difficile Infection Rates after Mandatory Hospital Public Reporting: Findings from a Longitudinal Cohort Study in Canada 
PLoS Medicine  2012;9(7):e1001268.
A population-based study conducted by Nick Daneman and colleagues in Ontario, Canada reports on the association between population reporting of hospital infection rates and a reduction in population burden of Clostridium difficile colitis.
The role of public reporting in improving hospital quality of care is controversial. Reporting of hospital-acquired infection rates has been introduced in multiple health care systems, but its relationship to infection rates has been understudied. Our objective was to determine whether mandatory public reporting by hospitals is associated with a reduction in hospital rates of Clostridium difficile infection.
Methods and Findings
We conducted a longitudinal, population-based cohort study in Ontario (Canada's largest province) between April 1, 2002, and March 31, 2010. We included all patients (>1 y old) admitted to 180 acute care hospitals. Using Poisson regression, we developed a model to predict hospital- and age-specific monthly rates of C. difficile disease per 10,000 patient-days prior to introduction of public reporting on September 1, 2008. We then compared observed monthly rates of C. difficile infection in the post-intervention period with rates predicted by the pre-intervention predictive model. In the pre-intervention period there were 33,634 cases of C. difficile infection during 39,221,113 hospital days, with rates increasing from 7.01 per 10,000 patient-days in 2002 to 10.79 in 2007. In the first calendar year after the introduction of public reporting, there was a decline in observed rates of C. difficile colitis in Ontario to 8.92 cases per 10,000 patient-days, which was significantly lower than the predicted rate of 12.16 (95% CI 11.35–13.04) cases per 10,000 patient-days (p<0.001). Over this period, public reporting was associated with a 26.7% (95% CI 21.4%–31.6%) reduction in C. difficile cases, or a projected 1,970 cases averted per year (95% CI 1,476–2,500). The effect was specific to C. difficile, with rates of community-acquired gastrointestinal infections and urinary tract infections unchanged. A limitation of our study is that this observational study design cannot rule out the influence of unmeasured temporal confounders.
Public reporting of hospital C. difficile rates was associated with a substantial reduction in the population burden of this infection. Future research will be required to discern the direct mechanism by which C. difficile infection rates may have been reduced in response to public reporting.
Please see later in the article for the Editors' Summary
Editors' Summary
A stay in hospital can be lifesaving but can expose people to health care–associated infections. One of these—Clostridium difficile infection—is a major cause of infectious disease illness and death in developed countries. C. difficile bacteria cause diarrhea and, more rarely, life-threatening inflammation of the gut (colitis). They are present in the gut of about 3% of adults but do not normally cause any problems because other “good” bacteria keep them in check. However, antibiotics destroy these good bacteria, and if a person who has taken antibiotics becomes infected with C. difficile before good bacteria repopulate the gut, C. difficile can multiply rapidly and produce toxins that cause illness. Because C. difficile is usually acquired from other infected patients and their contaminated environments, and because antibiotic use is highly prevalent in hospitals, most C. difficile infections are acquired in hospitals and nursing homes. Infections can be prevented by practicing good hygiene in health care environments (for example, washing hands regularly with soap and water), by isolating patients who are infected with C. difficile, and by prescribing antibiotics for other infections sparingly.
Why Was This Study Done?
Hospitals often need encouragement to improve infection control and other aspects of care. One potential way to improve the quality of hospital care is mandatory public reporting of measures of care quality. This intervention may help hospitals identify areas of poor performance to target for improvement or may motivate them to improve care quality to avoid the shame of a bad performance report. Although many health care systems have introduced public reporting of hospital-acquired infections, the effects of this intervention have been poorly studied. In this longitudinal cohort study, the researchers use population-based health care data to evaluate the impact of the introduction of mandatory hospital public reporting of the rates of hospital-acquired C. difficile infection in Ontario, Canada. Since September 1, 2008, hospitals in Ontario have been required to send monthly data on hospital-acquired C. difficile infections to the Ontario Ministry of Health and Long-Term Care for posting on a public website.
What Did the Researchers Do and Find?
The researchers used health care administrative data for all patients older than one year admitted to acute care hospitals in Ontario between April 1, 2002, and March 31, 2010, to develop a model to predict monthly rates of C. difficile disease per 10,000 patient-days based on rates in the period before the introduction of public reporting. They then compared the observed rates of C. difficile disease after the introduction of public reporting with the rates predicted by this model. In the pre-intervention period, there were nearly 34,000 cases of C. difficile disease during about 39 million hospital days. Rates of C. difficile disease increased from 7.01 cases per 10,000 patient-days in 2002 to 10.79 cases per 10,000 patient-days in 2007. After the introduction of public reporting, the C. difficile disease rate fell to 8.92 cases per 10,000 patient-days, which is significantly (that is, unlikely to have occurred by chance) lower than the 12.16 cases per 10,000 patient-days predicted by the pre-intervention model. Finally, the researchers estimate that public reporting was associated with a 26.6% reduction in C. difficile disease cases and that it averted about 1,900 cases per year.
What Do These Findings Mean?
These findings suggest that mandatory public reporting of hospital rates of C. difficile disease may reduce the population burden of this serious infection. Because this is an observational study, these findings do not prove that the introduction of mandatory public reporting actually caused a reduction in infection rates. Some other uncharacterized factor might be responsible for the decrease in C. difficile disease in Ontario hospitals since late 2008. Moreover, the many assumptions included in the predictive model means that the estimated number of cases averted by the introduction of public reporting may be inaccurate. Although further research is needed to determine how public reporting might affect C. difficile disease rates, the researchers suggest that, in this study, mandatory public reporting may have increased the prominence of C. difficile on hospital quality improvement agendas and may have motivated hospitals to adhere more closely to best practices in C. difficile prevention.
Additional Information
Please access these websites via the online version of this summary at
The US Centers for Disease Control and Prevention provides detailed information about C. difficile infection, including an article called Making Health Care Safer: Stopping C. difficile Infections
The UK National Health Service Choices website provides information about C. difficile infections
The Health Protection Agency provides information about mandatory reporting of C. difficile infections in England and Wales and a fact sheet on C. difficile
Information about public reporting of hospital C. difficile rates in Ontario is available (in English and French)
MedlinePlus provides links to further resources about C. difficile infections (in English and Spanish)
The UK Clostridium Difficle Support website has a forum containing personal stories about C. difficile infection
PMCID: PMC3398960  PMID: 22815656
17.  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
18.  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
19.  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
20.  “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
21.  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
22.  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
23.  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
24.  Evaluation of Molecular Assays for Rapid Detection of Methicillin-Resistant Staphylococcus aureus ▿ †  
Journal of Clinical Microbiology  2010;48(12):4598-4601.
The diagnostic sensitivities of the BD GeneOhm and Cepheid Xpert assays were compared using culture on log-serial dilutions of well-characterized methicillin-resistant Staphylococcus aureus (MRSA) and non-MRSA strains and on nasal and groin swabs from patients with histories of MRSA carriage. The sensitivities of GeneOhm and Xpert were high at 103-CFU/ml MRSA concentrations (92.3% and 96.3%, respectively) although decreased considerably (<35%) at a 1-log-lower concentration. Unexpectedly, both assays also detected select coagulase-negative staphylococci, which requires further evaluation.
PMCID: PMC3008470  PMID: 20943869
25.  A Call for Action: The Application of the International Health Regulations to the Global Threat of Antimicrobial Resistance 
PLoS Medicine  2011;8(4):e1001022.
Stephen Harbarth and colleagues argue that the International Health Regulations (IHR) should be applied to the global health threat of antimicrobial resistance.
PMCID: PMC3079636  PMID: 21526227

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