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1.  Epidemiology of end-stage renal disease in the countries of the Gulf Cooperation Council: a systematic review 
JRSM Short Reports  2012;3(6):38.
To describe the epidemiology of end stage renal disease (ESRD).
Mixed-methods systematic review.
The countries of the Gulf Cooperation Council (GCC) which consist of Saudi Arabia, the United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman.
Defined to have ESRD or patients on regular dialysis for a minimum dialysis period of at least three months. Since many outcomes were reviewed, studies that estimated the incidence and prevalence of ESRD as outcomes should not have defined the study population as ESRD population or patients on regular dialysis. Studies where the study population mainly comprised children or pregnant woman were excluded.
Main outcome measures
The trends of the incidence, prevalence, and mortality rate of ESRD; also, causes of mortality, primary causes and co-morbid conditions associated with ESRD.
44 studies included in this review show that the incidence of ESRD has increased while the prevalence and mortality rate of ESRD in the GCC has not been reported sufficiently. The leading primary causes of ESRD recorded in the countries of the GCC is diabetes with the most prevalent co-morbid conditions being Hypertension and Hepatitis C Virus infection; the most common cause of death was cardiovascular disease and sepsis.
This review highlights that the lack of national renal registries data is a critical issue in the countries of the GCC. The available data also do not provide an accurate and updated estimate for relevant outcomes. Additionally, considering the increasing burden of chronic kidney disease (CKD), these results stressed the needs and the importance of preventative strategies for leading causes of ESRD. Furthermore, more studies are needed to describe the epidemiology of ESRD and for assessing the overall quality of renal care.
PMCID: PMC3386663  PMID: 22768372
2.  Biomedical Publications Profile and Trends in Gulf Cooperation Council Countries 
There is a dearth of studies examining the relationship between research output and other socio-demographic indicators in the Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). The three interrelated aims of this study were, first, to ascertain the number of biomedical publications in the GCC from 1970 to 2010; second, to establish the rate of publication according population size during the same period and, third, to gauge the relationship between the number of publications and specific socio-economic parameters.
The Medline database was searched in October 2010 by affiliation, year and publication type from 1970 to 2010. Data obtained were normalised to the number of publications per million of the population, gross domestic product, and the number of physicians in each country.
The number of articles from the GCC region published over this 40 year period was 25,561. Saudi Arabia had the highest number followed by Kuwait, UAE, and then Oman. Kuwait had the highest profile of publication when normalised to population size, followed by Qatar. Oman is the lowest in this ranking. Overall, the six countries showed a rising trend in publication numbers with Oman having a significant increase from 1990 to 2005. There was a significant relationship between the number of physicians and the number of publications.
The research productivity from GGC has experienced complex and fluctuating growth in the past 40 years. Future prospects for increasing research productivity are discussed with particular reference to the situation in Oman.
PMCID: PMC3286715  PMID: 22375257
Publications; Oman; Gulf Cooperation Council; Arabian peninsula; Biomedical research
3.  Prevalences of overweight, obesity, hyperglycaemia, hypertension and dyslipidaemia in the Gulf: systematic review 
JRSM Short Reports  2011;2(7):55.
To examine the prevalence of risk factors for diabetes and its complications in the Co-operation Council of the Arab States of the Gulf (GCC) region.
Systematic review.
Co-operation Council of the Arab States of the Gulf (GCC) states (United Arab Emirates, Bahrain, Saudi Arabia, Oman, Qatar, Kuwait).
Residents of the GCC states participating in studies on the prevalence of overweight and obesity, hyperglycaemia, hypertension and dyslipidaemia.
Main outcome measures
Prevalences of overweight, obesity and hyperglycaemia, hypertension and hyperlipidaemia.
Forty-five studies were included in the review. Reported prevalences of overweight and obesity in adults were 25–50% and 13–50%, respectively. Prevalence appeared higher in women and to hold a non-linear association with age. Current prevalence of impaired glucose tolerance was estimated to be 10–20%. Prevalence appears to have been increasing in recent years. Estimated prevalences of hypertension and dyslipidaemia were few and used varied definitions of abnormality, making review difficult, but these also appeared to be high and increasing,
There are high prevalences of risk factors for diabetes and diabetic complications in the GCC region, indicative that their current management is suboptimal. Enhanced management will be critical if escalation of diabetes-related problems is to be averted as industrialization, urbanization and changing population demographics continue.
PMCID: PMC3147233  PMID: 21847437
4.  Antimicrobial resistance in Libya: 1970–2011 
The Libyan Journal of Medicine  2013;8:10.3402/ljm.v8i0.20567.
Resistance to antimicrobial agents is a major health problem that affects the whole world. Providing information on the past state of antimicrobial resistance in Libya may assist the health authorities in addressing the problem more effectively in the future. Information was obtained mainly from Highwire Press (including PubMed) search for the period 1970–2011 using the terms ‘antibiotic resistance in Libya’, ‘antimicrobial resistance in Libya’, ‘tuberculosis in Libya’, and ‘primary and acquired resistance in Libya’ in title and abstract. From 1970 to 2011 little data was available on antimicrobial resistance in Libya due to lack of surveillance and few published studies. Available data shows high resistance rates for Salmonella species in the late 1970s and has remained high to the present day. High prevalence rates (54–68%) of methicillin-resistant Staphylococcus aureus (MRSA) were reported in the last decade among S. aureus from patients with burns and surgical wound infections. No reports were found of vancomycin-resistant S. aureus (VRSA) or vancomycin-intermediate-resistant S. aureus (VISA) using standard methods from Libya up to the end of 2011. Reported rates of primary (i.e. new cases) and acquired (i.e. retreatment cases) multidrug-resistant tuberculosis (MDR-TB) from the eastern region of Libya in 1971 were 16.6 and 33.3% and in 1976 were 8.6 and 14.7%, in western regions in 1984–1986 were 11 and 21.5% and in the whole country in 2011 were estimated at 3.4 and 29%, respectively. The problem of antibiotic resistance is very serious in Libya. The health authorities in particular and society in general should address this problem urgently. Establishing monitoring systems based on the routine testing of antimicrobial sensitivity and education of healthcare workers, pharmacists, and the community on the health risks associated with the problem and benefits of prudent use of antimicrobials are some steps that can be taken to tackle the problem in the future.
PMCID: PMC3610430  PMID: 23537612
antibiotic resistance; enteric bacteria; methicillin-resistant Staphylococcus aureus; multidrug-resistant tuberculosis; Libya
5.  Seatbelt compliance and mortality in the Gulf Cooperation Council countries in comparison with other high-income countries 
Annals of Saudi Medicine  2011;31(4):347-350.
Mortality from road traffic collisions (RTC) is a major problem in the Gulf Cooperation Council (GCC) countries. Low compliance with seatbelt usage can be a contributing factor for increased mortality. The present study aimed to ascertain the presence of a relationship between seatbelt non-compliance of vehicle occupants and mortality rates in the GCC countries versus other high-income countries.
Observational and descriptive study using information published by the World Health Organization
Data for all GCC countries (n=6) and other high-income countries (n=37) were retrieved and compared with regard to population, gross national income, number of vehicles, seatbelt non-compliance and road traffic death rates. Univariate and multivariate analysis were used to define factors affecting the mortality rates.
The median road traffic death rates, occupant death rates, and the percentage of seatbelt non-compliance were significantly higher in the GCC countries (P<.0001, P=.02, P<.001, respectively). There was a strong correlation between occupant death rates and seatbelt non-compliance (R=.52, P=.008). Seatbelt non-compliance percentage was the only significant factor predicting mortality in the multiple linear regression model (P=.015).
Seatbelt non-compliance percentages in the GCC countries are significantly higher than in other high-income countries. This is a contributing factor in the increased road traffic collision mortality rate in these countries. Enforcement of seatbelt usage by law should be mandatory so as to reduce the toll of death of RTC in the GCC countries.
PMCID: PMC3156508  PMID: 21808108
6.  Incidence of Stomach Cancer in Oman and the Other Gulf Cooperation Council Countries 
Oman Medical Journal  2011;26(4):258-262.
Stomach cancer is the most common cancer among males in Oman and the second most frequent among females from 1997 to 2007. Reports have suggested the rate is higher in Oman than in the other GCC countries. This study aims to describe the epidemiology of stomach cancer in Oman and to explore the apparent differences in the incidence of stomach cancer between Oman and the other Gulf Cooperation Council (GCC) countries.
Data were obtained from the Omani National Cancer Registry (1997 - 2007) and from Gulf Centre for Cancer Registration reports (1998 - 2004).
The annual average age-adjusted incidence rates for stomach cancer in Oman were 10.1 per 100,000 for males and 5.6 per 100,000 for females between 1997 and 2007. The age-adjusted incidence varied by region within Oman, and the incidence rate was higher in Oman than in most other GCC countries between 1998 and 2004.
Further investigation of the completeness and accuracy of cancer registration is essential for exploration of variations in stomach cancer rates in the GCC countries.
PMCID: PMC3191710  PMID: 22043430
Oman; Stomach cancer; Epidemiology; Incidence; Gulf Cooperation Council
7.  Different recommendations for empiric first-choice antibiotic treatment of uncomplicated urinary tract infections in Europe 
Uncomplicated urinary tract infection (uUTI) is a common reason for antibiotic treatment in primary health care. Due to the increasing prevalence of antibiotic-resistant uropathogens it is crucial to use the most appropriate antibiotics for first-choice empiric treatment of uUTI. Particularly, it is important to avoid antibiotics associated with a high rate of antimicrobial resistance. This study compares national recommendations from six European countries, investigating recommendations for first-choice antibiotic therapy of uUTI.
General practice in six European countries.
Searches were undertaken on PubMed, the Cochrane Library databases, Google, and Google Scholar. Recommendations from different geographical regions in Europe were investigated: Northern Europe (Denmark, Sweden), Western Europe (Scotland), Central Europe (Germany), Southern Europe (Spain), and Eastern Europe (Croatia).
The six countries recommended seven different antibiotics. Five countries recommended more than one antibiotic as first-choice treatment. Half of the countries recommended antibiotics associated with a high rate (> 10–20%) of resistant E. coli. All countries recommended at least one antibiotic associated with a low (< 5%) resistance rate.
The differences in first-choice treatment of uUTI could not be explained by differences in local bacterial aetiology or by different patterns of antimicrobial resistance. Despite resistance rates exceeding 10–20%, sulphamethizole, trimethoprim. or fluoroquinolones were recommended in half of the countries.
Within the European countries there are considerable differences in recommendations for empiric first-choice antibiotic treatment of uUTI. In order to reduce the increasing antimicrobial resistance in Europe, it is important to agree on the most appropriate antibiotics for empiric treatment of uUTI.
PMCID: PMC3860300  PMID: 24102498
Antibiotics; antimicrobial resistance; Denmark; general practice; primary health care; recommendations; uncomplicated urinary tract infection
8.  Antimicrobial stewardship 
Virulence  2013;4(2):151-157.
Antimicrobial stewardship is an emerging field currently defined by a series of strategies and interventions aimed toward improving appropriate prescription of antibiotics in humans in all healthcare settings. The ultimate goal is the preservation of current and future antibiotics against the threat of antimicrobial resistance, although improving patient safety and reducing healthcare costs are important concurrent aims. Prospective audit and feedback interventions are probably the most widely practiced of all antimicrobial stewardship strategies. Although labor-intensive, they are more easily accepted by physicians compared with formulary restriction and preauthorization strategies and have a higher potential for educational opportunities. Objective evaluation of antimicrobial stewardship is critical for determining the success of such programs. Nonetheless, there is controversy over which outcomes to measure and there is a pressing need for novel study designs that can objectively assess antimicrobial stewardship interventions despite the limitations inherent in the structure of most such programs.
PMCID: PMC3654615  PMID: 23302793
antimicrobial stewardship; prospective audit and feedback; antimicrobial resistance; antibiotics; cost effectiveness; quasi-experimental study design
9.  Prevalence of Type 2 Diabetes in the States of The Co-Operation Council for the Arab States of the Gulf: A Systematic Review 
PLoS ONE  2012;7(8):e40948.
The recent and ongoing worldwide expansion in prevalence of Type 2 Diabetes (T2DM) is a considerable risk to individuals, health systems and economies. The increase in prevalence has been particularly marked in the states of the Co-operation Council for the Arab States of the Gulf (GCC), and these trends are set to continue. We aimed to systematically review the current prevalence of T2DM within these states, and also within particular sub-populations.
We identified 27 published studies for review. Studies were identified by systematic database searches. Medline and Embase were searched using terms such as diabetes mellitus, non-insulin-dependent, hyperglycemia, prevalence, epidemiology and Gulf States. Our search also included scanning reference lists, contacting experts and hand-searching key journals. Studies were judged against pre-determined inclusion and exclusion criteria, and where suitable for inclusion, data extraction and quality assessment was achieved using a specifically-designed tool. All studies where prevalence of diabetes was investigated were eligible for inclusion. The inclusion criteria required that the study population be of a GCC country, but otherwise all ages, sexes and ethnicities were included, resident and migrant populations, urban and rural, of all socioeconomic and educational backgrounds. No limitations on publication type, publication status, study design or language of publication were imposed. However, we did not include secondary reports of data, such as review articles without novel data synthesis.
The prevalence ofT2DM is an increasing problem for all GCC states. They may therefore benefit to a relatively high degree from co-ordinated implementation of broadly consistent management strategies. Further study of prevalence in children and in national versus expatriate populations would also be useful.
PMCID: PMC3414510  PMID: 22905094
10.  Regulatory Aspects of Pharmaceuticals’ Exports in Gulf Cooperation Council Countries 
The Gulf cooperation council (GCC) region is considered as “Emerging market” for pharmaceutical export and bilateral trade. The understanding of the regulatory requirements of this region can be beneficial for pharmaceutical export. Some incidents of the year 2008-09, like recession or economic slowdown in highly well-off and regulated market of the EU and US, raised the demand for alternate destinations for business. The regulations of Gulf countries are encouraging the import of quality generic products, which can be good news to the Indian drug manufacturers.
PMCID: PMC3122046  PMID: 21731362
Exports; Gulf cooperation council; pharmaceutical; regulatory
11.  Health Alliance for prudent antibiotic prescribing in patients with respiratory tract infections (HAPPY AUDIT) -impact of a non-randomised multifaceted intervention programme 
BMC Family Practice  2011;12:52.
Excessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance.
GPs from two Nordic countries, two Baltic Countries and two Hispano-American countries registered patients with respiratory tract infections (RTIs) in 2008 and 2009. After first registration they received individual prescriber feedback and they were offered an intervention programme that included training courses, clinical guidelines, posters for waiting rooms, patient brochures and access to point of care tests (Strep A and C-Reactive Protein). Antibiotic prescribing rates were compared before and after the intervention.
A total of 440 GPs registered 47011 consultations; 24436 before the intervention (2008) and 22575 after the intervention (2009). After the intervention, the GPs significantly reduced the percentage of consultations resulting in an antibiotic prescription. In patients with lower RTI the GPs in Lithuania reduced the prescribing rate by 42%, in Russia by 25%, in Spain by 25%, and in Argentina by 9%. In patients with upper RTIs, the corresponding reductions in the antibiotic prescribing rates were in Lithania 20%, in Russia 15%, in Spain 9%, and in Argentina 5%.
A multifaceted intervention programme targeting GPs and patients and focusing on improving diagnostic procedures in patients with RTIs may lead to a marked reduction in antibiotic prescribing. The pragmatic before-after design used may suffer from some limitations and the reduction in antibiotic prescribing could be influenced by factors not related to the intervention.
PMCID: PMC3146837  PMID: 21689406
12.  A Situational Analysis of Antimicrobial Drug Resistance in Africa: Are We Losing the Battle? 
The first arrival of a sizable shipment of penicillin at the North African Theatre of Operations for USA military use in 1943 was a landmark that turned a new chapter of antibiotic use in Africa. Over the past decade the expansion of resources and the technological advances have meant that much larger quantities of drugs are available in developing countries than ever before. As a result, many more individuals are receiving necessary treatment or therapy than just ten years ago. This very welcome event is accompanied by the terrible irony that increases in drug availability and use can promote drug resistance and render the same life-saving drugs ineffective.
The study focused on bacterial pathogens. One hundred and three relevant literatures were identified from the PubMed online database. The coverage included research articles concerning antimicrobial resistance involving subjects of an African country.
Resistant bacteria are on a war path and evidently have acquired an edge over us. Our actions are evidently fuelling the resistance. The indiscriminate use of antibiotics in humans and livestock, wrong and substandard prescriptions by unqualified ‘medical personnel’ together with poor diagnosis or lack of it are all adding fuel to the already fired train of resistant microbes.
To win the war and turn tables as we did with the discovery of penicillin and other antimicrobials in the 1940s, then we must all act now. Antimicrobial stewardship programs-Education, training of laboratory personnel and investment in laboratory infrastructure development are desirable in these situations
PMCID: PMC3407837  PMID: 22876078
Antibiotics; Resistance; Bacteria
13.  Antimicrobial resistance gene distribution: a socioeconomic and sociocultural perspective 
The appearance of resistance to many first-line antimicrobial agents presents a critical challenge to the successful treatment of bacterial infections. Antimicrobial resistant bacteria and resistance genes are globally distributed, but significant variations in prevalence have been observed in different geographical regions. This article discusses possible relationships between socioeconomic and sociocultural factors and regional differences in the prevalence of antibiotic-resistant bacteria and their associated resistance genes. Findings indicate that the few studies that have been conducted to understand relationships between socioeconomic and sociocultural factors and antimicrobial resistance have focused on patterns of phenotypic antibiotic resistance. Yet, a critical need exists for molecular studies of human influences on bacterial resistance and adaptation. We propose that the results of these studies, coupled with well-coordinated culturally appropriate interventions that address specific socioeconomic and sociocultural needs may be necessary to reduce the scourge of antimicrobial resistance in both developing and developed countries.
PMCID: PMC2831251  PMID: 20204098
antimicrobial resistant bacteria; resistance genes; gene distribution; socioeconomic; sociocultural
14.  Growing Problem of Multidrug-Resistant Enteric Pathogens in Africa 
Emerging Infectious Diseases  2007;13(11):1640-1646.
A disproportionate number of low-income persons are affected.
Control of fecal–orally transmitted pathogens is inadequate in many developing countries, in particular, in sub-Saharan Africa. Acquired resistance to antimicrobial drugs is becoming more prevalent among Vibrio cholerae, Salmonella enteritidis, diarrheagenic Escherichia coli, and other pathogens in this region. The poor, who experience most of the infections caused by these organisms, bear the brunt of extended illness and exacerbated proportion of deaths brought about by resistance. Improved antimicrobial drug stewardship is an often cited, but inadequately implemented, intervention for resistance control. Resistance containment also requires improvements in infectious disease control, access to and quality assurance of antimicrobial agents, as well as diagnostic facilities. Structural improvements along these lines will also enhance disease prevention and control as well as rational antimicrobial drug use. Additionally, more research is needed to identify low-cost, high-impact interventions for resistance control.
PMCID: PMC3375797  PMID: 18217545
enteric pathogens; antimicrobial resistance; antibiotic resistance; sub-Saharan Africa; perspective
15.  Antimicrobial Use and Antimicrobial Resistance: A Population Perspective 
Emerging Infectious Diseases  2002;8(4):347-354.
The need to stem the growing problem of antimicrobial resistance has prompted multiple, sometimes conflicting, calls for changes in the use of antimicrobial agents. One source of disagreement concerns the major mechanisms by which antibiotics select resistant strains. For infections like tuberculosis, in which resistance can emerge in treated hosts through mutation, prevention of antimicrobial resistance in individual hosts is a primary method of preventing the spread of resistant organisms in the community. By contrast, for many other important resistant pathogens, such as penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium resistance is mediated by the acquisition of genes or gene fragments by horizontal transfer; resistance in the treated host is a relatively rare event. For these organisms, indirect, population-level mechanisms of selection account for the increase in the prevalence of resistance. These mechanisms can operate even when treatment has a modest, or even negative, effect on an individual host’s colonization with resistant organisms.
PMCID: PMC2730242  PMID: 11971765
Antimicrobial resistance; population dynamics; mathematical model; infectious disease transmission; ecological study; epidemiologic methods
16.  Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States 
Antimicrobial resistance is an under-appreciated threat to public health in nations around the globe. With globalization booming, it is important to understand international patterns of resistance. If countries already experience similar patterns of resistance, it may be too late to worry about international spread. If large countries or groups of countries that are likely to leap ahead in their integration with the rest of the world – China being the standout case – have high and distinctive patterns of resistance, then a coordinated response could substantially help to control the spread of resistance. The literature to date provides only limited evidence on these issues.
We study the recent patterns of antibiotic resistance in three geographically separated, and culturally and economically distinct countries – China, Kuwait and the United States – to gauge the range and depth of this global health threat, and its potential for growth as globalization expands. Our primary measures are the prevalence of resistance of specific bacteria to specific antibiotics. We also propose and illustrate methods for aggregating specific "bug-drug" data. We use these aggregate measures to summarize the resistance pattern for each country and to study the extent of correlation between countries' patterns of drug resistance.
We find that China has the highest level of antibiotic resistance, followed by Kuwait and the U.S. In a study of resistance patterns of several most common bacteria in China in 1999 and 2001, the mean prevalence of resistance among hospital-acquired infections was as high as 41% (with a range from 23% to 77%) and that among community- acquired infections was 26% (with a range from 15% to 39%). China also has the most rapid growth rate of resistance (22% average growth in a study spanning 1994 to 2000). Kuwait is second (17% average growth in a period from 1999 to 2003), and the U.S. the lowest (6% from 1999 to 2002). Patterns of resistance across the three countries are not highly correlated; the most correlated were China and Kuwait, followed by Kuwait and the U.S., and the least correlated pair was China and the U.S.
Antimicrobial resistance is a serious and growing problem in all three countries. To date, there is not strong international convergence in the countries' resistance patterns. This finding may change with the greater international travel that will accompany globalization. Future research on the determinants of drug resistance patterns, and their international convergence or divergence, should be a priority.
PMCID: PMC1502134  PMID: 16603071
17.  Carbapenem Restriction and its Effect on Bacterial Resistance in an Intensive Care unit of a Teaching Hospital  
Development of antibiotic resistance in Intensive Care Units (ICUs) is a worldwide problem. The purpose of this study was to evaluate the effect of an antibiotic stewardship program (ASP) by carbapenems restriction on gram-negative antimicrobial resistance in ICU. The study was designed in a 21 bedded general ICU of a teaching hospital with two wings (one and two) in Tehran, Iran. Carbapenem prescription in ICU1 was restricted to only the culture proven multi-drug-resistant bacteria with the absence of sensitivity to other antimicrobial agents. Carbapenem had to be prescribed by a trained ICU physician with close consultation with infectious disease specialist and the clinical pharmacist posted in ICU. Post-prescription reviews and de-escalations were carried out by the same team on regular basis. Restriction policy was commenced in January 2011 in ICU1. All documented infections and resistance patterns of isolated pathogens were recorded in both ICUs during two periods of 6 months before and 9 months after restriction policy implementation. During this study bacterial growth was detected in 51.5% of 1601 samples. Carbapenem administration was decreased from 6.86 to 2.75 DDD/100 patients day (60% decreases) pre-restriction and post-restriction respectively. Significant increase in sensitivity of pseudomonas to imipenem was observed in ICU1 comparing with pre-restriction period six months post restriction (p = 0.000). Sensitivity of Klebsiella and Acinetobacter to imipenem did not change significantly during the study period. Conclusion: Our study demonstrated that restriction of carbapenems can increase sensitivity of P. aeroginosa to imipenem.
PMCID: PMC3813286  PMID: 24250656
18.  Extreme Antimicrobial Peptide and Polymyxin B Resistance in the Genus Burkholderia 
Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance.
PMCID: PMC3143681  PMID: 21811491
Burkholderia; antimicrobial peptides; polymyxin; outer membrane; lipopolysaccharide; antibiotics; bacterial resistance mechanisms
19.  Extreme Antimicrobial Peptide and Polymyxin B Resistance in the Genus Burkholderia 
Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance.
PMCID: PMC3417367  PMID: 22919572
Burkholderia; antimicrobial peptides; polymyxin; outer membrane; lipopolysaccharide; antibiotics; bacterial resistance mechanisms
20.  Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital 
Antimicrobial stewardship has not always prevailed in a wide variety of medical institutions in Japan.
The infection control team was involved in the review of individual use of antibiotics in all inpatients (6348 and 6507 patients/year during the first and second annual interventions, respectively) receiving intravenous antibiotics, according to the published guidelines, consultation with physicians before prescription of antimicrobial agents and organisation of education programme on infection control for all medical staff. The outcomes of extensive implementation of antimicrobial stewardship were evaluated from the standpoint of antimicrobial use density, treatment duration, duration of hospital stay, occurrence of antimicrobial-resistant bacteria and medical expenses.
Prolonged use of antibiotics over 2 weeks was significantly reduced after active implementation of antimicrobial stewardship (2.9% vs. 5.2%, p < 0.001). Significant reduction in the antimicrobial consumption was observed in the second-generation cephalosporins (p = 0.03), carbapenems (p = 0.003), aminoglycosides (p < 0.001), leading to a reduction in the cost of antibiotics by 11.7%. The appearance of methicillin-resistant Staphylococcus aureus and the proportion of Serratia marcescens to Gram-negative bacteria decreased significantly from 47.6% to 39.5% (p = 0.026) and from 3.7% to 2.0% (p = 0.026), respectively. Moreover, the mean hospital stay was shortened by 2.9 days after active implementation of antimicrobial stewardship.
Extensive implementation of antimicrobial stewardship led to a decrease in the inappropriate use of antibiotics, saving in medical expenses, reduction in the development of antimicrobial resistance and shortening of hospital stay.
PMCID: PMC3469737  PMID: 22846073
Increased temperature and other environmental effects of global climate change (GCC) have documented impacts on many species (e.g., polar bears, amphibians, coral reefs) as well as on ecosystem processes and species interactions (e.g., the timing of predator–prey interactions). A challenge for ecotoxicologists is to predict how joint effects of climatic stress and toxicants measured at the individual level (e.g., reduced survival and reproduction) will be manifested at the population level (e.g., population growth rate, extinction risk) and community level (e.g., species richness, food-web structure). The authors discuss how population- and community-level responses to toxicants under GCC are likely to be influenced by various ecological mechanisms. Stress due to GCC may reduce the potential for resistance to and recovery from toxicant exposure. Long-term toxicant exposure can result in acquired tolerance to this stressor at the population or community level, but an associated cost of tolerance may be the reduced potential for tolerance to subsequent climatic stress (or vice versa). Moreover, GCC can induce large-scale shifts in community composition, which may affect the vulnerability of communities to other stressors. Ecological modeling based on species traits (representing life-history traits, population vulnerability, sensitivity to toxicants, and sensitivity to climate change) can be a promising approach for predicting combined impacts of GCC and toxicants on populations and communities. Environ. Toxicol. Chem. 2013;32:49–61. © 2012 SETAC
PMCID: PMC3601420  PMID: 23147390
Ecological risk assessment; Stressor interaction; Population ecotoxicology; Community ecotoxicology; Cost of adaptation
22.  Principles and Strategies of Antimicrobial Stewardship in the Neonatal Intensive Care Unit 
Seminars in perinatology  2012;36(6):431-436.
The judicious use of antibiotics is an important means to limit the emergence of antibiotic resistant organisms. While specific guidelines for neonates are often lacking, antibiotic stewardship principles can be applied to the neonatal intensive care unit. Principles include accurately identifying patients who need antibiotic therapy, using local epidemiology to guide the selection of empiric therapy, avoiding agents with overlapping activity, adjusting antibiotics when cultures results become available, monitoring for toxicity, and optimizing the dose, route, and duration of therapy. Neonatal intensive care units should develop interdisciplinary antimicrobial stewardship teams with the support of their institutions. Prescriber audit and feedback as well as preauthorization and formulary restriction of selected antibiotics are recommended antimicrobial stewardship interventions. Ancillary strategies include education and computerized decision support. Metrics to evaluate antimicrobial stewardship programs should include measurements of patient safety and quality, such as rates of adverse drug events, and appropriate dosing and timing of perioperative prophylaxis.
PMCID: PMC3509381  PMID: 23177802
23.  Antimicrobial Resistance in Asia: Current Epidemiology and Clinical Implications 
Infection & Chemotherapy  2013;45(1):22-31.
Antimicrobial resistance has become one of the most serious public health concerns worldwide. Although circumstances may vary by region or country, it is clear that some Asian countries are epicenters of resistance, having seen rapid increases in the prevalence of antimicrobial resistance of major bacterial pathogens. In these locations, however, the public health infrastructure to combat this problem is very poor. The prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA), macrolide-resistant Streptococcus pneumoniae, and multidrug-resistant enteric pathogens are very high due to the recent emergence of extremely drug-resistant gram-negative bacilli in Asia. Because antimicrobial options for these pathogens are extremely limited, infections caused by antimicrobial-resistant bacteria are often associated with inappropriate antimicrobial therapy and poor clinical outcomes. Physicians should be aware of the current epidemiological status of resistance and understand the appropriate use of antimicrobial agents in clinical practice. This review focuses on describing the epidemiology and clinical implications of antimicrobial-resistant bacterial infections in Asian countries.
PMCID: PMC3780932  PMID: 24265947
Antimicrobial resistance; Epidemiology; Bacterial infections; Asia
24.  Implementation of an antimicrobial stewardship program on the medical-surgical service of a 100-bed community hospital 
Antimicrobial stewardship has been promoted as a key strategy for coping with the problems of antimicrobial resistance and Clostridium difficile. Despite the current call for stewardship in community hospitals, including smaller community hospitals, practical examples of stewardship programs are scarce in the reported literature. The purpose of the current report is to describe the implementation of an antimicrobial stewardship program on the medical-surgical service of a 100-bed community hospital employing a core strategy of post-prescriptive audit with intervention and feedback.
For one hour twice weekly, an infectious diseases physician and a clinical pharmacist audited medical records of inpatients receiving systemic antimicrobial therapy and made non-binding, written recommendations that were subsequently scored for implementation. Defined daily doses (DDDs; World Health Organization Center for Drug Statistics Methodology) and acquisition costs per admission and per patient-day were calculated monthly for all administered antimicrobial agents.
The antimicrobial stewardship team (AST) made one or more recommendations for 313 of 367 audits during a 16-month intervention period (September 2009 – December 2010). Physicians implemented recommendation(s) from each of 234 (75%) audits, including from 85 of 115 for which discontinuation of all antimicrobial therapy was recommended. In comparison to an 8-month baseline period (January 2009 – August 2009), there was a 22% decrease in defined daily doses per 100 admissions (P = .006) and a 16% reduction per 1000 patient-days (P = .013). There was a 32% reduction in antimicrobial acquisition cost per admission (P = .013) and a 25% acquisition cost reduction per patient-day (P = .022).
An effective antimicrobial stewardship program was implemented with limited resources on the medical-surgical service of a 100-bed community hospital.
PMCID: PMC3499185  PMID: 23043720
Antimicrobial stewardship; ASP; Small community hospital
25.  Relationship of Carbapenem Restriction in 22 University Teaching Hospitals to Carbapenem Use and Carbapenem-Resistant Pseudomonas aeruginosa▿  
Many hospital antimicrobial stewardship programs restrict the availability of selected drugs by requiring prior approval. Carbapenems may be among the restricted drugs, but it is unclear if hospitals that restrict availability actually use fewer carbapenems than hospitals that do not restrict use. Nor is it clear if restriction is related to resistance. We evaluated the relationship between carbapenem restriction and the volume of carbapenem use and both the incidence rate and proportion of carbapenem-resistant Pseudomonas aeruginosa isolates from 2002 through 2006 in a retrospective, longitudinal, multicenter analysis among a consortium of academic health centers. Carbapenem use was measured from billing records as days of therapy per 1,000 patient days. Hospital antibiograms were used to determine both the incidence rate and proportion of carbapenem-resistant P. aeruginosa isolates. A survey inquired about restriction policies for antibiotics, including carbapenems. General linear mixed models were used to examine study outcomes. Among 22 hospitals with sufficient data for analysis, overall carbapenem use increased significantly over the 5 years of study (P < 0.0001), although overall carbapenem resistance in P. aeruginosa did not change. Hospitals that restricted carbapenems (n = 8; 36%) used significantly fewer carbapenems (P = 0.04) and reported lower incidence rates of carbapenem-resistant P. aeruginosa (P = 0.01) for all study years. Fluoroquinolone use was a potential confounder of these relationships, but hospitals that restricted carbapenems actually used fewer fluoroquinolones than those that did not. Restriction of carbapenems is associated with both lower use and lower incidence rates of carbapenem resistance in P. aeruginosa.
PMCID: PMC2681502  PMID: 19273670

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