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1.  Noma Affected Children from Niger Have Distinct Oral Microbial Communities Based on High-Throughput Sequencing of 16S rRNA Gene Fragments 
We aim to understand the microbial ecology of noma (cancrum oris), a devastating ancient illness which causes severe facial disfigurement in>140,000 malnourished children every year. The cause of noma is still elusive. A chaotic mix of microbial infection, oral hygiene and weakened immune system likely contribute to the development of oral lesions. These lesions are a plausible entry point for unidentified microorganisms that trigger gangrenous facial infections. To catalog bacteria present in noma lesions and identify candidate noma-triggering organisms, we performed a cross-sectional sequencing study of 16S rRNA gene amplicons from sixty samples of gingival fluid from twelve healthy children, twelve children suffering from noma (lesion and healthy sites), and twelve children suffering from Acute Necrotizing Gingivitis (ANG) (lesion and healthy sites). Relative to healthy individuals, samples taken from lesions in diseased mouths were enriched with Spirochaetes and depleted for Proteobacteria. Samples taken from healthy sites of diseased mouths had proportions of Spirochaetes and Proteobacteria that were similar to healthy control individuals. Samples from noma mouths did not have a higher abundance of Fusobacterium, casting doubt on its role as a causative agent of noma. Microbial communities sampled from noma and ANG lesions were dominated by the same Prevotella intermedia OTU, which was much less abundant in healthy sites sampled from the same mouths. Multivariate analysis confirmed that bacterial communities in healthy and lesion sites were significantly different. Several OTUs in the Orders Erysipelotrichales, Clostridiales, Bacteroidales, and Spirochaetales were identified as indicators of noma, suggesting that one or more microbes within these Orders is associated with the development of noma lesions. Future studies should include longitudinal sampling of viral and microbial components of this community, before and early in noma lesion development.
Author Summary
Noma is a traumatic disease characterized by oral-facial lesions that often lead to severe disfigurement and ultimately shame and isolation from the community. Because the causes of noma are likely to be numerous, and reaching those who suffer from this illness is challenging, the etiology of noma remains ill-defined. Although it is known that oral hygiene and nutrition influence the development of noma, evidence suggests that one or more microbes play a crucial role in development of noma lesions. Previous studies have examined the DNA of microbes in lesions to determine which species are present and how their abundances differ between healthy mouth sites and noma lesions. These studies used techniques that were state-of-the-art at the time, though we know they likely only scratched the surface of the resident microbial diversity. Here we extend these studies by digging deeper to characterize a larger diversity of microbial species in noma and control samples, with the goal of better identifying which microbes are uniquely present or have altered abundances in noma lesions.
PMCID: PMC4256271  PMID: 25474262
2.  Efficacy of a New Educational Tool to Improve Handrubbing Technique amongst Healthcare Workers: A Controlled, Before-After Study 
PLoS ONE  2014;9(9):e105866.
Hand hygiene is a key component of infection control in healthcare. WHO recommends that healthcare workers perform six specific poses during each hand hygiene action. SureWash (Glanta Ltd, Dublin, Ireland) is a novel device that uses video-measurement technology and immediate feedback to teach this technique. We assessed the impact of self-directed SureWash use on healthcare worker hand hygiene technique and evaluated the device's diagnostic capacity.
A controlled before-after study: subjects in Group A were exposed to the SureWash for four weeks followed by Group B for 12 weeks. Each subject's hand hygiene technique was assessed by blinded observers at baseline (T0) and following intervention periods (T1 and T2). Primary outcome was performance of a complete hand hygiene action, requiring all six poses during an action lasting ≥20 seconds. The number of poses per hand hygiene action (maximum 6) was assessed in a post-hoc analysis. SureWash's diagnostic capacity compared to human observers was assessed using ROC curve analysis.
Thirty-four and 29 healthcare workers were recruited to groups A and B, respectively. No participants performed a complete action at baseline. At T1, one Group A participant and no Group B participants performed a complete action. At baseline, the median number of poses performed per action was 2.0 and 1.0 in Groups A and B, respectively (p = 0.12). At T1, the number of poses per action was greater in Group A (post-intervention) than Group B (control): median 3.8 and 2.0, respectively (p<0.001). In Group A, the number of poses performed twelve weeks post-intervention (median 3.0) remained higher than baseline (p<0.001). The area under the ROC curves for the 6 poses ranged from 0.59 to 0.88.
While no impact on complete actions was demonstrated, SureWash significantly increased the number of poses per hand hygiene action and demonstrated good diagnostic capacity.
PMCID: PMC4152219  PMID: 25180508
3.  Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later 
Intensive Care Medicine  2014;40(10):1429-1448.
For decades, clinicians dealing with immunocompromised and critically ill patients have perceived a link between Candida colonization and subsequent infection. However, the pathophysiological progression from colonization to infection was clearly established only through the formal description of the colonization index (CI) in critically ill patients. Unfortunately, the literature reflects intense confusion about the pathophysiology of invasive candidiasis and specific associated risk factors.
We review the contribution of the CI in the field of Candida infection and its development in the 20 years following its original description in 1994. The development of the CI enabled an improved understanding of the pathogenesis of invasive candidiasis and the use of targeted empirical antifungal therapy in subgroups of patients at increased risk for infection.
The recognition of specific characteristics among underlying conditions, such as neutropenia, solid organ transplantation, and surgical and nonsurgical critical illness, has enabled the description of distinct epidemiological patterns in the development of invasive candidiasis.
Despite its limited bedside practicality and before confirmation of potentially more accurate predictors, such as specific biomarkers, the CI remains an important way to characterize the dynamics of colonization, which increases early in patients who develop invasive candidiasis.
PMCID: PMC4176828  PMID: 24934813
Candida albicans; Candidemia; Invasive candidiasis; Colonization; Colonization index; Empirical treatment; Nosocomial infections
4.  Status of the implementation of the World Health Organization multimodal hand hygiene strategy in United States of America health care facilities 
The World Health Organization (WHO) launched a multimodal strategy and campaign in 2009 to improve hand hygiene practices worldwide. Our objective was to evaluate the implementation of the strategy in United States health care facilities.
From July through December 2011, US facilities participating in the WHO global campaign were invited to complete the Hand Hygiene Self-Assessment Framework online, a validated tool based on the WHO multimodal strategy.
Of 2,238 invited facilities, 168 participated in the survey (7.5%). A detailed analysis of 129, mainly nonteaching public facilities (80.6%), showed that most had an advanced or intermediate level of hand hygiene implementation progress (48.9% and 45.0%, respectively). The total Hand Hygiene Self-Assessment Framework score was 36 points higher for facilities with staffing levels of infection preventionists > 0.75/100 beds than for those with lower ratios (P = .01) and 41 points higher for facilities participating in hand hygiene campaigns (P = .002).
Despite the low response rate, the survey results are unique and allow interesting reflections. Whereas the level of progress of most participating facilities was encouraging, this may reflect reporting bias, ie, better hospitals more likely to report. However, even in respondents, further improvement can be achieved, in particular by embedding hand hygiene in a stronger institutional safety climate and optimizing staffing levels dedicated to infection prevention. These results should encourage the launch of a coordinated national campaign and higher participation in the WHO global campaign.
PMCID: PMC4047653  PMID: 24581011
WHO multimodal strategy; Health care-associated infection; Infection control; US hospitals; WHO Hand Hygiene Self-Assessment Framework
5.  Prevalence of nosocomial infections and anti-infective therapy in Benin: results of the first nationwide survey in 2012 
Data on nosocomial infections in hospitals in low-income countries are scarce and often inconsistent. The objectives of this study were to estimate the prevalence of nosocomial infections and antimicrobial drug use in Benin hospitals.
All hospitals were invited to participate in the first national point prevalence study conducted between 10–26 October 2012 using the protocol developed by the “Hospitals in Europe Link for Infection Control through Surveillance” (HELICS) project. Infection prevalence rates and the proportion of infected patients and exposure to antimicrobials were assessed.
Overall, 87% (39/45) of hospitals participated. Of 3130 inpatients surveyed, 972 nosocomial infections were identified among 597 patients, representing an overall prevalence of infected patients of 19.1%. The most frequent infections were related to the urinary tract (48.2%), vascular catheter use (34.7%), and surgical site (24.7%). 64.6% of patients surveyed were treated with antibiotics, including a significant proportion (30%) of non-infected patients and a high proportion of self-medication (40.8%). Resistance of leading nosocomial pathogens to antimicrobials included methicillin-resistance (52.5%) among Staphylococcus aureus, vancomycin resistance among enterococci (67.5%), cefotaxime resistance among Escherichia coli (67.6%), and ceftazidime resistance among Acinetobacter baumannii (100%) and Pseudomonas aeruginosa (68.2%).
Benin has high nosocomial infection rates and calls for the implementation of new national infection control policies. Patient safety education and training of all individuals involved in healthcare delivery will be critical to highlight awareness of the burden of disease. The high use of antimicrobials needs to be addressed, particularly their indiscriminate use in non-infected patients.
PMCID: PMC4039045  PMID: 24883183
Nosocomial infection; Prevalence; Antimicrobial resistance; Co-morbidity; Antibiotic use; Infection control; National surveillance; Surveillance; Africa; Low-/middle-income countries
6.  Hospital-Wide Multidisciplinary, Multimodal Intervention Programme to Reduce Central Venous Catheter-Associated Bloodstream Infection 
PLoS ONE  2014;9(4):e93898.
Central line-associated bloodstream infection (CLABSI) is the major complication of central venous catheters (CVC). The aim of the study was to test the effectiveness of a hospital-wide strategy on CLABSI reduction. Between 2008 and 2011, all CVCs were observed individually and hospital-wide at a large university-affiliated, tertiary care hospital. CVC insertion training started from the 3rd quarter and a total of 146 physicians employed or newly entering the hospital were trained in simulator workshops. CVC care started from quarter 7 and a total of 1274 nurses were trained by their supervisors using a web-based, modular, e-learning programme. The study included 3952 patients with 6353 CVCs accumulating 61,366 catheter-days. Hospital-wide, 106 patients had 114 CLABSIs with a cumulative incidence of 1.79 infections per 100 catheters. We observed a significant quarterly reduction of the incidence density (incidence rate ratios [95% confidence interval]: 0.92 [0.88–0.96]; P<0.001) after adjusting for multiple confounders. The incidence densities (n/1000 catheter-days) in the first and last study year were 2.3/1000 and 0.7/1000 hospital-wide, 1.7/1000 and 0.4/1000 in the intensive care units, and 2.7/1000 and 0.9/1000 in non-intensive care settings, respectively. Median time-to-infection was 15 days (Interquartile range, 8-22). Our findings suggest that clinically relevant reduction of hospital-wide CLABSI was reached with a comprehensive, multidisciplinary and multimodal quality improvement programme including aspects of behavioural change and key principles of good implementation practice. This is one of the first multimodal, multidisciplinary, hospital-wide training strategies successfully reducing CLABSI.
PMCID: PMC3979709  PMID: 24714418
7.  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
8.  Strengthening the evidence-policy interface for patient safety: enhancing global health through hospital partnerships 
Strengthening the evidence-policy interface is a well-recognized health system challenge in both the developed and developing world. Brokerage inherent in hospital-to-hospital partnerships can boost relationships between “evidence” and “policy” communities and move developing countries towards evidence based patient safety policy. In particular, we use the experience of a global hospital partnership programme focused on patient safety in the African Region to explore how hospital partnerships can be instrumental in advancing responsive decision-making, and the translation of patient safety evidence into health policy and planning. A co-developed approach to evidence-policy strengthening with seven components is described, with reflections from early implementation. This rapidly expanding field of enquiry is ripe for shared learning across continents, in keeping with the principles and spirit of health systems development in a globalized world.
PMCID: PMC3842804  PMID: 24131652
Patient safety; Global health; Policy-making; Evidence-based practice; Africa; Hospitals
9.  Transmission dynamics of methicillin-resistant Staphylococcus aureus in a medical intensive care unit 
Intensive care units (ICUs) play an important role in the epidemiology of methicillin-resistant Staphyloccocus aureus (MRSA). Although successful interventions are multi-modal, the relative efficacy of single measures remains unknown. We developed a discrete time, individual-based, stochastic mathematical model calibrated on cross-transmission observed through prospective surveillance to explore the transmission dynamics of MRSA in a medical ICU. Most input parameters were derived from locally acquired data. After fitting the model to the 46 observed cross-transmission events and performing sensitivity analysis, several screening and isolation policies were evaluated by simulating the number of cross-transmissions and isolation-days. The number of all cross-transmission events increased from 54 to 72 if only patients with a past history of MRSA colonization are screened and isolated at admission, to 75 if isolation is put in place only after the results of the admission screening become available, to 82 in the absence of admission screening and with a similar reactive isolation policy, and to 95 when no isolation policy is in place. The method used (culture or polymerase chain reaction) for admission screening had no impact on the number of cross-transmissions. Systematic regular screening during ICU stay provides no added-value, but aggressive admission screening and isolation effectively reduce the number of cross-transmissions. Critically, colonized healthcare workers may play an important role in MRSA transmission and their screening should be reinforced.
PMCID: PMC3427499  PMID: 22572025
methicillin-resistant Staphyloccocus aureus; epidemiology; mathematical modelling
10.  Microarray Analysis of Microbiota of Gingival Lesions in Noma Patients 
Noma (cancrum oris) is a gangrenous disease of unknown etiology affecting the maxillo-facial region of young children in extremely limited resource countries. In an attempt to better understand the microbiological events occurring during this disease, we used phylogenetic and low-density microarrays targeting the 16S rRNA gene to characterize the gingival flora of acute noma and acute necrotizing gingivitis (ANG) lesions, and compared them to healthy control subjects of the same geographical and social background. Our observations raise doubts about Fusobacterium necrophorum, a previously suspected causative agent of noma, as this species was not associated with noma lesions. Various oral pathogens were more abundant in noma lesions, notably Atopobium spp., Prevotella intermedia, Peptostreptococcus spp., Streptococcus pyogenes and Streptococcus anginosus. On the other hand, pathogens associated with periodontal diseases such as Aggregatibacter actinomycetemcomitans, Capnocytophaga spp., Porphyromonas spp. and Fusobacteriales were more abundant in healthy controls. Importantly, the overall loss of bacterial diversity observed in noma samples as well as its homology to that of ANG microbiota supports the hypothesis that ANG might be the immediate step preceding noma.
Author Summary
Noma, or cancrum oris, is a mutilating disease affecting children in extremely limited-resource countries, suffering poor hygiene and chronic malnutrition. This devastating gangrenous disease affects the hard and soft tissues of the face. To date, the origin of the disease is still debated and current hypotheses rely on microbial diseases or on the immunologic status of the host. In an attempt to better understand the etiology of noma, the authors of the study used microarrays to assess the bacterial microbiota of gingival fluids sampled from 413 healthy and diseased children. Results obtained show reduced bacterial diversity and abundance in samples obtained from diseased patients compared to samples obtained from healthy donors, sharing identical social situation. Oral pathogens were found in both conditions but Fusobacterium necrophorum, a putative causative agent of noma, was not associated with the disease. On the other hand, no clear bacterial candidate could be identified as the etiological agent of the disease. However, a number of potential pathogens were found at higher abundance in disease patients compared to healthy donors. Finally, this study provides evidence that acute necrotizing gingivitis often evolves to noma, an observation of importance considering the dramatic condition of patients evolving to acute noma.
PMCID: PMC3784469  PMID: 24086784
11.  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
12.  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
13.  Implementation of infection control best practice in intensive care units throughout Europe: a mixed-method evaluation study 
The implementation of evidence-based infection control practices is essential, yet challenging for healthcare institutions worldwide. Although acknowledged that implementation success varies with contextual factors, little is known regarding the most critical specific conditions within the complex cultural milieu of varying economic, political, and healthcare systems. Given the increasing reliance on unified global schemes to improve patient safety and healthcare effectiveness, research on this topic is needed and timely. The ‘InDepth’ work package of the European FP7 Prevention of Hospital Infections by Intervention and Training (PROHIBIT) consortium aims to assess barriers and facilitators to the successful implementation of catheter-related bloodstream infection (CRBSI) prevention in intensive care units (ICU) across several European countries.
We use a qualitative case study approach in the ICUs of six purposefully selected acute care hospitals among the 15 participants in the PROHIBIT CRBSI intervention study. For sensitizing schemes we apply the theory of diffusion of innovation, published implementation frameworks, sensemaking, and new institutionalism. We conduct interviews with hospital health providers/agents at different organizational levels and ethnographic observations, and conduct rich artifact collection, and photography during two rounds of on-site visits, once before and once one year into the intervention. Data analysis is based on grounded theory. Given the challenge of different languages and cultures, we enlist the help of local interpreters, allot two days for site visits, and perform triangulation across multiple data sources.
Qualitative measures of implementation success will consider the longitudinal interaction between the initiative and the institutional context. Quantitative outcomes on catheter-related bloodstream infections and performance indicators from another work package of the consortium will produce a final mixed-methods report.
A mixed-methods study of this scale with longitudinal follow-up is unique in the field of infection control. It highlights the ‘Why’ and ‘How’ of best practice implementation, revealing key factors that determine success of a uniform intervention in the context of several varying cultural, economic, political, and medical systems across Europe. These new insights will guide future implementation of more tailored and hence more successful infection control programs.
Trial registration
Trial number: PROHIBIT-241928 (FP7 reference number)
PMCID: PMC3584730  PMID: 23421909
Implementation; Infection control; Catheter-related bloodstream infections; Hand hygiene; Intensive care units; Best practice; Organizational culture; Organizational case studies; Organizational innovation; Organizational decision making; Patient safety
14.  High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study 
Exposure to urinary catheters is considered the most important risk factor for healthcare-associated urinary tract infection (UTI) and is associated with significant morbidity and substantial extra-costs. In this study, we assessed the impact of urinary catheterisation (UC) on symptomatic healthcare-associated UTI among hospitalized patients.
A nationwide period prevalence survey of healthcare-associated infections was conducted during 1 May to 30 June 2004 in 49 Swiss hospitals and included 8169 adult patients (4313 female; 52.8%) hospitalised in medical, surgical, intermediate, and intensive care wards. Additional data were collected on exposure to UC to investigate factors associated with UTI among hospitalised adult patients exposed and non-exposed to UC.
1917 (23.5%) patients were exposed to UC within the week prior to survey day; 126 (126/8169; 1.5%) developed UTI. Exposure to UC preceded UTI only in 73 cases (58%). By multivariate logistic regression analysis, UTI was independently associated with exposure to UC (odds ratio [OR], 3.9 [95% CI, 2.6-5.9]), female gender (OR, 2.1 [95% CI, 1.4-3.1]), an American Society of Anesthesiologists’ score > 2 points (OR, 3.2 [95% CI, 1.1-9.4], and prolonged hospital stay >20 days (OR, 1.9 [95% CI, 1.4-3.2]. Further analysis showed that the only significant factor for UTI with exposure to UC use was prolonged hospital stay >40 days (OR, 2.9 [95% CI, 1.3-6.1], while female gender only showed a tendency (OR, 1.6 [95% CI, 1.0-2.7]. In the absence of exposure to UC, the only significant risk factor for UTI was female gender (OR, 3.3 [95% CI, 1.7-6.5]).
Exposure to UC was the most important risk factor for symptomatic healthcare-associated UTI, but only concerned about half of all patients with UTI. Further investigation is warranted to improve overall infection control strategies for UTI.
PMCID: PMC3598194  PMID: 23391300
Prevalence; Urinary catheter; Acute care; Urinary tract infection; Nosocomial; Risk factors
15.  Access to antibiotics: a safety and equity challenge for the next decade 
Bacterial resistance to antibiotics is increasing worldwide in healthcare settings and in the community. Some microbial pathogens have become resistant to multiple antibiotics, if not all presently available, thus severely compromising treatment success and contributing to enhanced morbidity, mortality, and resource use. The major driver of resistance is misuse of antibiotics in both human and non-human medicine. Both enhanced access and restricted use in many parts of the world is mandatory. There is an urgent need for an international, integrated, multi-level action to preserve antibiotics in the armamentarium of the 21st century and address the global issue of antimicrobial resistance.
PMCID: PMC3599140  PMID: 23305311
Antibiotics; Antimicrobial resistance; Antimicrobial resistance surveillance; Antibiotics – use; Multidrug-resistant organisms
16.  Clinical and Nonclinical Health Care Workers Faced a Similar Risk of Acquiring 2009 Pandemic H1N1 Infection 
(See the editorial commentary by Drumright and Holmes, on pages 284–286.)
Reporting of confirmed pandemic influenza A virus (pH1N1) 2009 infection was mandatory among health care workers in Hong Kong. Among 1158 confirmed infections, there was no significant difference in incidence among clinical versus nonclinical staff (relative risk, 0.98; 95% confidence interval, 0.78–1.20). Reported community exposure to pH1N1 was common and was similar in both groups.
PMCID: PMC3202320  PMID: 21765076
17.  Developed-developing country partnerships: Benefits to developed countries? 
Developing countries can generate effective solutions for today’s global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed—this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and developing countries.
PMCID: PMC3459713  PMID: 22709651
Developed countries; Developing countries; Partnerships; Learning; International cooperation; Health care quality, Global health
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.  Bacterial Diversity in Oral Samples of Children in Niger with Acute Noma, Acute Necrotizing Gingivitis, and Healthy Controls 
Noma is a gangrenous disease that leads to severe disfigurement of the face with high morbidity and mortality, but its etiology remains unknown. Young children in developing countries are almost exclusively affected. The purpose of the study was to record and compare bacterial diversity in oral samples from children with or without acute noma or acute necrotizing gingivitis from a defined geographical region in Niger by culture-independent molecular methods.
Methods and Principal Findings
Gingival samples from 23 healthy children, nine children with acute necrotizing gingivitis, and 23 children with acute noma (both healthy and diseased oral sites) were amplified using “universal” PCR primers for the 16 S rRNA gene and pooled according to category (noma, healthy, or acute necrotizing gingivitis), gender, and site status (diseased or control site). Seven libraries were generated. A total of 1237 partial 16 S rRNA sequences representing 339 bacterial species or phylotypes at a 98–99% identity level were obtained. Analysis of bacterial composition and frequency showed that diseased (noma or acute necrotizing gingivitis) and healthy site bacterial communities are composed of similar bacteria, but differ in the prevalence of a limited group of phylotypes. Large increases in counts of Prevotella intermedia and members of the Peptostreptococcus genus are associated with disease. In contrast, no clear-cut differences were found between noma and non-noma libraries.
Similarities between acute necrotizing gingivitis and noma samples support the hypothesis that the disease could evolve from acute necrotizing gingivitis in certain children for reasons still to be elucidated. This study revealed oral microbiological patterns associated with noma and acute necrotizing gingivitis, but no evidence was found for a specific infection-triggering agent.
Author Summary
Noma is a devastating gangrenous disease that leads to severe facial disfigurement, but its cause remains unknown. It is associated with high morbidity and mortality and affects almost exclusively young children living in remote areas of developing countries, particularly in Africa. Several factors have been linked to the disease, including malnutrition, immune dysfunction, lack of oral hygiene, and lesions of the mucosal gingival barrier, particularly the presence of acute necrotizing gingivitis, and a potentially non-identified bacterial factor acting as a trigger for the disease. This study assessed the total bacterial diversity present in 69 oral samples of 55 children in Niger with or without acute noma or acute necrotizing gingivitis using culture-independent molecular methods. Analysis of bacterial composition and frequency showed that diseased and healthy site bacterial communities are composed of similar bacteria, but differ in the prevalence of a limited group of phylotypes. We failed to identify a causative infectious agent for noma or acute necrotizing gingivitis as the most plausible pathogens for both conditions were present also in sizeable numbers in healthy subjects. Most likely, the disease is initiated by a synergistic combination of several bacterial species, and not a single agent.
PMCID: PMC3295795  PMID: 22413030
21.  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
23.  Patient Participation: Current Knowledge and Applicability to Patient Safety 
Mayo Clinic Proceedings  2010;85(1):53-62.
Patient participation is increasingly recognized as a key component in the redesign of health care processes and is advocated as a means to improve patient safety. The concept has been successfully applied to various areas of patient care, such as decision making and the management of chronic diseases. We review the origins of patient participation, discuss the published evidence on its efficacy, and summarize the factors influencing its implementation. Patient-related factors, such as acceptance of the new patient role, lack of medical knowledge, lack of confidence, comorbidity, and various sociodemographic parameters, all affect willingness to participate in the health care process. Among health care workers, the acceptance and promotion of patient participation are influenced by other issues, including the desire to maintain control, lack of time, personal beliefs, type of illness, and training in patient-caregiver relationships. Social status, specialty, ethnic origin, and the stakes involved also influence patient and health care worker acceptance. The London Declaration, endorsed by the World Health Organization World Alliance for Patient Safety, calls for a greater role for patients to improve the safety of health care worldwide. Patient participation in hand hygiene promotion among staff to prevent health care—associated infection is discussed as an illustrative example. A conceptual model including key factors that influence participation and invite patients to contribute to error prevention is proposed. Further research is essential to establish key determinants for the success of patient participation in reducing medical errors and in improving patient safety.
PMCID: PMC2800278  PMID: 20042562
24.  Cockroaches (Ectobius vittiventris) in an Intensive Care Unit, Switzerland1 
Emerging Infectious Diseases  2009;15(3):496-497.
PMCID: PMC2666288  PMID: 19239776
Infestation; cockroach; intensive care unit; infection control; Ectobius vittiventris; Switzerland; letter
25.  Novel Microarray Design Strategy To Study Complex Bacterial Communities▿  
Assessing bacterial flora composition appears to be of increasing importance to fields as diverse as physiology, development, medicine, epidemiology, the environment, and the food industry. We report here the development and validation of an original microarray strategy that allows analysis of the phylogenic composition of complex bacterial mixtures. The microarray contains ∼9,500 feature elements targeting 16S rRNA gene-specific regions. Probe design was performed by selecting oligonucleotide sequences specific to each node of the seven levels of the bacterial phylogenetic tree (domain, phylum, class, order, family, genus, and species). This approach, based on sequence information, allows analysis of the bacterial contents of complex bacterial mixtures to detect both known and unknown microorganisms. The presence of unknown organisms can be suspected and mapped on the phylogenetic tree, indicating where to refine analysis. Initial proof-of-concept experiments were performed on oral bacterial communities. Our results show that this hierarchical approach can reveal minor changes (≤1%) in gingival flora content when samples collected in individuals from similar geographical origins are compared.
PMCID: PMC2268287  PMID: 18203854

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