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1.  β-Lactamase Production in Key Gram-Negative Pathogen Isolates from the Arabian Peninsula 
Clinical Microbiology Reviews  2013;26(3):361-380.
SUMMARY
Infections due to Gram-negative bacilli (GNB) are a leading cause of morbidity and mortality worldwide. The extent of antibiotic resistance in GNB in countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain, has not been previously reviewed. These countries share a high prevalence of extended-spectrum-β-lactamase (ESBL)- and carbapenemase-producing GNB, most of which are associated with nosocomial infections. Well-known and widespread β-lactamases genes (such as those for CTX-M-15, OXA-48, and NDM-1) have found their way into isolates from the GCC states. However, less common and unique enzymes have also been identified. These include PER-7, GES-11, and PME-1. Several potential risk factors unique to the GCC states may have contributed to the emergence and spread of β-lactamases, including the unnecessary use of antibiotics and the large population of migrant workers, particularly from the Indian subcontinent. It is clear that active surveillance of antimicrobial resistance in the GCC states is urgently needed to address regional interventions that can contain the antimicrobial resistance issue.
doi:10.1128/CMR.00096-12
PMCID: PMC3719487  PMID: 23824364
2.  Epidemiology of end-stage renal disease in the countries of the Gulf Cooperation Council: a systematic review 
JRSM Short Reports  2012;3(6):38.
Objectives
To describe the epidemiology of end stage renal disease (ESRD).
Design
Mixed-methods systematic review.
Setting
The countries of the Gulf Cooperation Council (GCC) which consist of Saudi Arabia, the United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman.
Participants
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.
Results
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.
Conclusions
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.
doi:10.1258/shorts.2012.011150
PMCID: PMC3386663  PMID: 22768372
3.  Biomedical Publications Profile and Trends in Gulf Cooperation Council Countries 
Objectives
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.
Methods:
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.
Results:
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.
Conclusion:
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
4.  Prevalences of overweight, obesity, hyperglycaemia, hypertension and dyslipidaemia in the Gulf: systematic review 
JRSM Short Reports  2011;2(7):55.
Objectives
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.
Design
Systematic review.
Setting
Co-operation Council of the Arab States of the Gulf (GCC) states (United Arab Emirates, Bahrain, Saudi Arabia, Oman, Qatar, Kuwait).
Participants
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.
Results
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,
Conclusions
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.
doi:10.1258/shorts.2011.011019
PMCID: PMC3147233  PMID: 21847437
5.  Incidence of Stomach Cancer in Oman and the Other Gulf Cooperation Council Countries 
Oman Medical Journal  2011;26(4):258-262.
Objectives
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.
Methods
Data were obtained from the Omani National Cancer Registry (1997 - 2007) and from Gulf Centre for Cancer Registration reports (1998 - 2004).
Results
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.
Conclusion
Further investigation of the completeness and accuracy of cancer registration is essential for exploration of variations in stomach cancer rates in the GCC countries.
doi:10.5001/omj.2011.62
PMCID: PMC3191710  PMID: 22043430
Oman; Stomach cancer; Epidemiology; Incidence; Gulf Cooperation Council
6.  Epidemiology of headache in Arab countries 
The epidemiology of headache in Arab countries was systematically reviewed through Medline identification of four papers reporting headache prevalence in the Arab nations of Qatar, Saudi Arabia (2 papers) and Oman. The prevalence of headache varied from 8 to 12% in Saudi Arabia to 72.5% in Qatar and 83.6% in Oman. Headache was commoner in females and younger people. The prevalence of tension headache was 3.1–9.5% in Saudi Arabia and the 1-year prevalence in Qatar was 11.2%. The migraine prevalence was 2.6–5% in Saudi Arabia and 7.9% in Qatar, while the 1-year migraine prevalence was 10.1% in Oman. The results show a migraine prevalence within that estimated worldwide. However, it is clear that epidemiological data from Arab countries are lacking, and there is disparity in the reported prevalence from Saudi Arabia when compared with its two neighbours, Qatar and Oman. Wider study adopting the same methodology in the six Gulf countries (Saudi Arabia, Qatar, Oman, Bahrain, United Arab Emirates and Kuwait) is needed to examine variations in headache and migraine prevalence.
doi:10.1007/s10194-009-0173-8
PMCID: PMC3452181  PMID: 19949829
Headache; Migraine; Prevalence; Epidemiology; Arab countries
7.  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.
BACKGROUND AND OBJECTIVES:
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.
DESIGN AND SETTING:
Observational and descriptive study using information published by the World Health Organization
METHODS:
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.
RESULTS:
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).
CONCLUSIONS:
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.
doi:10.4103/0256-4947.83208
PMCID: PMC3156508  PMID: 21808108
8.  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.
Aims
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.
Methods
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.
Conclusions
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.
doi:10.1371/journal.pone.0040948
PMCID: PMC3414510  PMID: 22905094
9.  Mortality and Hospital Stay Associated with Resistant Staphylococcus aureus and Escherichia coli Bacteremia: Estimating the Burden of Antibiotic Resistance in Europe 
PLoS Medicine  2011;8(10):e1001104.
The authors calculate excess mortality, excess hospital stay, and related hospital expenditure associated with antibiotic-resistant bacterial bloodstream infections (Staphylococcus aureus and Escherichia coli) in Europe.
Background
The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS).
Methods and Findings
The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future.
Conclusions
Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Antimicrobial resistance—a consequence of the use and misuse of antimicrobial medicines—occurs when a microorganism becomes resistant (usually by mutation or acquiring a resistance gene) to an antimicrobial drug to which it was previously sensitive. Then standard treatments become ineffective, leading to persistent infections, which may spread to other people. With some notable exceptions such as TB, HIV, malaria, and gonorrhea, most of the disease burden attributable to antimicrobial resistance is caused by hospital-associated infections due to opportunistic bacterial pathogens. These bacteria often cause life-threatening or difficult-to-manage conditions such as deep tissue, wound, or bone infections, or infections of the lower respiratory tract, central nervous system, or blood stream. The two most frequent causes of blood stream infections encountered worldwide are Staphylococcus aureus and Escherichia coli.
Why Was This Study Done?
Although hospital-associated infections have gained much attention over the past decade, the overall effect of this growing phenomenon on human health and medical services has still to be adequately quantified. The researchers proposed to fill this information gap by estimating the impact—morbidity, mortality, and demands on health care services—of antibiotic resistance in Europe for two types of resistant organisms that are typically associated with resistance to multiple classes of antibiotics and can be regarded as surrogate markers for multi-drug resistance—methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli.
What Did the Researchers Do and Find?
Recently, the Burden of Resistance and Disease in European Nations project collected representative data on the clinical impact of antimicrobial resistance throughout Europe. Using and combining this information with 2007 prevalence data from the European Antibiotic Resistance Surveillance System, the researchers calculated the burden of disease associated with methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli blood stream infections. This burden of disease was expressed as excess number of deaths, excess number of days in hospital, and excess costs. Using statistical models, the researchers predicted trend-based resistance trajectories up to 2015 for the 31 participating countries in the European region.
The researchers included 1,293 hospitals from the 31 countries, typically covering 47% of all available acute care hospital beds in most countries, in their analysis. For S. aureus, the estimated number of blood stream infections totaled 108,434, of which 27,711 (25.6%) were methicillin-resistant. E. coli caused 163,476 blood stream infections, of which 15,183 (9.3%) were resistant to third-generation cephalosporins. An estimated 5,503 excess deaths were associated with blood stream infections caused by methicillin-resistant S. aureus (with the UK and France predicted to experience the highest excess mortality), and 2,712 excess deaths with blood stream infections caused by third-generation cephalosporin-resistant E. coli (predicted to be the highest in Turkey and the UK). The researchers also found that blood stream infections caused by both methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli contributed respective excesses of 255,683 and 120,065 extra bed-days, accounting for an estimated extra cost of 62.0 million Euros (92.8 million international dollars). In their trend analysis, the researchers found that 97,000 resistant blood stream infections and 17,000 associated deaths could be expected in 2015, along with increases in the lengths of hospital stays and costs. Importantly, the researchers estimated that in the near future, the burden of disease associated with third-generation cephalosporin-resistant E. coli is likely to surpass that associated with methicillin-resistant S. aureus.
What Do These Findings Mean?
These findings show that even though the blood stream infections studied represent only a fraction of the total burden of disease associated with antibiotic resistance, excess mortality associated with these infections caused by methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli is high, and the associated prolonged length of stays in hospital imposes a considerable burden on health care systems in Europe. Importantly, a possible shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections is concerning. Such forecasts suggest that despite anticipated gains in the control of methicillin-resistant S. aureus, the increasing number of infections caused by third-generation cephalosporin-resistant Gram-negative pathogens, such as E. coli, is likely to outweigh this achievement soon. This increasing burden will have a big impact on already stretched health systems.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001104.
The World Health Organization has a fact sheet on general antimicrobial resistance
The US Centers for Disease Control and Prevention webpage on antibiotic/antimicrobial resistance includes information on educational campaigns and resources
The European Centre for Disease Control provides data about the prevalence of resistance in Europe through an interactive database
doi:10.1371/journal.pmed.1001104
PMCID: PMC3191157  PMID: 22022233
10.  The Epidemiology of Acute Coronary Syndrome in Oman 
Objectives:
This study aimed to evaluate the epidemiology and coronary risk factors of acute coronary syndrome (ACS) in Oman.
Methods:
Data were collected through a prospective, multinational, multicentre survey of consecutive patients, hospitalised over a 5-month period in 2007 with a diagnosis of ACS, in Yemen and five Arabian Gulf countries (Oman, Bahrain, Kuwait, Qatar, United Arab Emirates). Here we present data of Omani patients aged ≥20 years who received a provisional diagnosis of ACS and were consequently admitted to 14 different hospitals.
Results:
There where 1,340 confirmed ACS episodes in 748 men and 592 women (median age 61 years). The overall crude incidence rate of ACS was 338.9 per 100,000 person-years (P-Y). The age-standardised rate (ASR) of ACS was 779 and 674 per 100,000 P-Y for men and women, respectively. The ASR male-to-female rate ratio was highest in the ST-elevation myocardial infarction (STEMI) group (2.26, 95% confidence interval ([CI], 1.63 to 3.15) followed by the non-STEMI (NSTEMI) group (1.68, 95% CI 1.28 to 2.21) and unstable angina (0.79, 95% CI 0.66 to 0.99). Unstable angina accounted for 55%, STEMI for 26% and NSTEMI for 19% of ACS cases. Among the coronary risk factors, there was a high prevalence of hypertension (68%), diabetes mellitus (DM) (36%), hyperlipidaemia (63%), and overweight/obesity (65%), with a relatively low rate of current tobacco use (11%).
Conclusion:
Our study confirms a high incidence of ACS in Omanis and supports the notion that the cardiovascular disease epidemic is also sweeping developing countries.
PMCID: PMC3616799  PMID: 23573381
Acute coronary syndrome; Incidence; Cardiovascular disease; Ischemic heart disease; Risk factors; Oman
11.  Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1744-8603-2-6
PMCID: PMC1502134  PMID: 16603071
12.  Can We Prevent Breast Cancer? 
Breast cancer is the second most common cancer in the world and the most common cancer in females accounting to 23% of all cases. Between January 1998 and December 2004–2004, 6,882 cases were reported from all GCC states accounting to 11.8% from all cancers and 22.7% from cancers in females. An ASR/100,000 woman was 46.4 from Bahrain, 44.3 from Kuwait, 35.5 from Qatar, 19.2 from UAE, 14.2 from Oman and 12.9 from KSA. Breast cancer is the most frequent cancer in Arab women constituting 14–42% of all women cancers. Breast cancer in Arab countries presents almost 10 yrs younger than in USA and Europe. Median age at presentation is 48–52 and 50% of all cases are below the age of 50 where as only 25% of cases in industrialized nations are below the age of 50 yrs. What we need to fight this deadly disease is opening of screening centers with trained physicians equipped with ultrasound, x-ray unit, a pathology lab and most of all a system where a patient is seen urgently on referral to a secondary level care. Health education campaigns should be organized, female medical students should be encouraged to be general surgeons in a community where social customs still have value.
PMCID: PMC3068727  PMID: 21475500
13.  New antibiotics for bad bugs: where are we? 
Bacterial resistance to antibiotics is growing up day by day in both community and hospital setting, with a significant impact on the mortality and morbidity rates and the financial burden that is associated. In the last two decades multi drug resistant microorganisms (both hospital- and community-acquired) challenged the scientific groups into developing new antimicrobial compounds that can provide safety in use according to the new regulation, good efficacy patterns, and low resistance profile. In this review we made an evaluation of present data regarding the new classes and the new molecules from already existing classes of antibiotics and the ongoing trends in antimicrobial development. Infectious Diseases Society of America (IDSA) supported a proGram, called “the ′10 × ´20′ initiative”, to develop ten new systemic antibacterial drugs within 2020. The microorganisms mainly involved in the resistance process, so called the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae) were the main targets. In the era of antimicrobial resistance the new antimicrobial agents like fifth generation cephalosporins, carbapenems, monobactams, β-lactamases inhibitors, aminoglycosides, quinolones, oxazolidones, glycopeptides, and tetracyclines active against Gram-positive pathogens, like vancomycin-resistant S. aureus (VRSA) and MRSA, penicillin-resistant streptococci, and vancomycin resistant Enterococcus (VRE) but also against highly resistant Gram-negative organisms are more than welcome. Of these compounds some are already approved by official agencies, some are still in study, but the need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections. Therefore the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance.
doi:10.1186/1476-0711-12-22
PMCID: PMC3846448  PMID: 23984642
New antibiotics; Resistance; Bacteria; FDA; EMA
14.  Epidemiology of Multi-Drug Resistant Organisms in a Teaching Hospital in Oman: A One-Year Hospital-Based Study 
The Scientific World Journal  2014;2014:157102.
Background. Antimicrobial resistance is increasingly recognized as a global challenge. A few studies have emerged on epidemiology of multidrug resistant organisms in tertiary care settings in the Arabian Gulf. Aim. To describe the epidemiology of multi-drug resistant organisms (MDRO) at Sultan Qaboos University Hospital, a tertiary hospital in Oman. Methods. A retrospective review of MDRO records has been conducted throughout the period from January 2012 till December 2012. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method. Results. Out of the total of 29,245 admissions, there have been 315 patients registered as MDRO patients giving an overall prevalence rate of 10.8 (95% CI 9.3, 12.4) MDRO cases per 1000 admissions. In addition, the prevalence rate of MDRO isolates was 11.2 (95% CI 9.7, 12.9) per 1000 admissions. Overall, increasing trends in prevalence rates of MDRO patients and MDRO isolates were observed throughout the study period. Conclusion. Antimicrobial resistance is an emerging challenge in Oman. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to prevent proliferation of MDRO. Along such quest, stringent antibiotic prescription guidelines are needed in the country.
doi:10.1155/2014/157102
PMCID: PMC3914445  PMID: 24526881
15.  Resistance of uropathogenic bacteria to first-line antibiotics in mexico city: A multicenter susceptibility analysis 
Abstract
Background
Growing antibiotic resistance demands the constant reassessment of antimicrobial efficacy, particularly in countries with wide antibiotic abuse, where higher resistance prevalence is often found. Knowledge of resistance trends is particularly important when prescribing antibiotics empirically, as is usually the case for urinary tract infections (UTIs). Currently, in Mexico City, ampicillin, cotrimoxazole (trimethoprim/sulfamethoxazole), and ciprofloxacin are used as “first-line” antibiotic treatment for UTI.
Objective
The aim of this study was to analyze the resistance of bacterial isolates to antibiotics, with a focus on first-line antibiotics, in Mexican pediatric patients and sexually active or pregnant female outpatients.
Methods
In this multicenter susceptibility analysis, bacterial isolates from urine samples collected from pediatric patients and sexually-active or pregnant female outpatients presenting with acute, uncomplicated UTIs in Mexico City from January 2006 through June 2006, were included in the study. Samples were tested for susceptibility to 10 antibiotics by the disk-diffusion method.
Results
Four-hundred and seventeen bacterial isolates were derived from sexually active or pregnant female outpatients (324 Escherichia coli) and pediatric patients (93 Klebsiella pneumoniae). We found a high prevalence of resistance towards the drugs used as “first-line” when treating UTIs: ampicillin, cotrimoxazole, and ciprofloxacin (79%, 60%, and 24% resistance, respectively). Ninety-eight percent of K pneumoniae isolates were resistant to ampicillin, whereas 66% of the E coli isolates were resistant to cotrimoxazole. Resistance towards third-generation cephalosporins was also high (6%–8% of E coli and 10%–28% of K pneumoniae). This was possibly caused by chromosomal β-lactamases, as 30% of all isolates were also resistant to amoxicillin/clavulanate. In contrast, 98% of the E coli isolates and 84% of the K pneumoniae strains (96% of all isolates) were found to be susceptible to nitrofurantoin, which has been in clinical use for much longer than most other drugs in this study.
Conclusion
In these urine samples from laboratories in Mexico City, resistance of K pneumoniae and E coli isolates to first-line treatment (ampicillin, cotrimoxazole, or ciprofloxacin) of UTI was high, whereas most E coli and K pneumoniae isolates were susceptible to nitrofurantoin and the fourth-generation cephalosporin cefepime. (Curr Ther Res Clin Exp. 2007;68:120–126) Copyright © 2007 Excerpta Medica, Inc.
doi:10.1016/j.curtheres.2007.03.005
PMCID: PMC3966000  PMID: 24678125
urinary tract infection; uropathogenic bacteria
16.  Nosocomial blood stream infection in intensive care units at Assiut University Hospitals (Upper Egypt) with special reference to extended spectrum β-lactamase producing organisms 
BMC Research Notes  2009;2:76.
Aim
This study investigated the nosocomial blood stream infection (BSI) in the adult ICUs in Assiut university hospitals to evaluate the rate of infection in different ICUs, causative microorganisms, antimicrobial resistance, outcome of infection, risk factors, prevalence of extended spectrum B-lactamase producing organisms and molecular typing of Klebsiella pneumoniae strains to highlight the role of environment as a potential source of nosocomial BSI.
Methods
This study was conducted over a period of 12 months from January 2006 to December 2006. All Patients admitted to the different adult ICUs were monitored daily by attending physicians for subsequent development of nosocomial BSI. Blood cultures were collected from suspected patients to detect the causative organisms. After antimicrobial susceptibility testing, detection of ESBLs was conducted among gram negative isolates. Klebsiella pneumoniae isolates were tested by PCR to determine the most common group of B-lactamase genes responsible for resistance. Klebsiella pneumoniae isolates from infected patients and those isolated from the environment were typed by RAPD technique to investigate the role of environment in transmission of infection.
Results
The study included 2095 patients who were admitted to different ICUs at Assiut University Hospitals from January 2006 to December 2006. Blood samples were collected from infected patients for blood cultures. The colonies were identified and antibiotic sensitivities were performed. This study showed that the rate of nosocomial BSI was 75 per 1000 ICU admissions with the highest percentages in Trauma ICU (17%). Out of 159 patients with primary bloodstream infection, 61 patients died representing a crude mortality rate of 38%. Analysis of the organisms causing BSI showed that Gram positive organisms were reported in 69.1% (n = 121); MRSA was the most prevalent (18.9%), followed by methicillin resistant coagulase negative Staphylococci (16%). Gram negative bacilli were reported in 29.1% (n = 51). In this case, Klebsiella pneumoniae was the most common (10.3%) followed E coli (8.6%). Candida spp. was reported only in (1.7%) of isolates. Antibiotics sensitivities of Gram positive organisms showed that these organisms were mostly sensitive to vancomycin (90.1%), while Gram negative organisms were mostly sensitive to imipenem (90.2%). In this study we tested Gram negative isolates for the production of the ESBL enzyme and concluded that 64.7% (33/51) of patients' isolates and 20/135 (14.8%) environmental isolates were confirmed to be ESBL producers. The type of β-lactamase gene was determined by polymerase chain reaction which showed that SHV was the main type. Molecular typing was done for 18 Klebsiella pneumoniae strains that caused nosocomial BSI and for the 36 Klebsiella pneumoniae strains which were isolated from the environmental samples by the RAPD method. The two environmental strains were identical, with one isolated from a patient, which confirms the serious role of the hospital environment in the spread of infections.
Conclusion
Nosocomial BSI represents a current problem in Assiut University Hospitals, Egypt. Problems associated with BSI include infection with multidrug resistant pathogens (especially ESBLs) which are difficult to treat and are associated with increased mortality. Of all available anti-microbial agents, carbapenems are the most active and reliable treatment options for infections caused by ESBL isolates. However, overuse of carbapenems may lead to resistance of other Gram-negative organisms.
doi:10.1186/1756-0500-2-76
PMCID: PMC2694819  PMID: 19419535
17.  Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial 
PLoS Medicine  2010;7(12):e1000377.
Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities.
Background
It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities.
Methods and Findings
In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1–10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%–8.9%) at baseline, to 46.9% (37.5%–57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%–13.3%) at month 12, significantly lower than the treated group (p<0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%–4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year.
Conclusions
This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections.
Trial registration
www.ClinicalTrials.gov NCT00322972
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 1928, Alexander Fleming discovered penicillin, the first antibiotic (a drug that kills bacteria). By the early 1940s, scientists were able to make large quantities of penicillin and, in the following decades, several other classes of powerful antibiotics were discovered. For example, erythromycin—the first macrolide antibiotic—was developed in the early 1950s. For a time, it looked like bacteria and the diseases that they cause had been defeated. But bacteria rapidly become resistant to antibiotics. Under the “selective pressure” of an antibiotic, bacteria that have acquired a random change in their DNA that allows them to survive in the antibiotic's presence outgrow nonresistant bacteria. What's more, bacteria can transfer antibiotic resistance genes between themselves. Nowadays, antibiotic resistance is a major public health concern. Almost every type of disease-causing bacteria has developed resistance to one or more antibiotic in clinical use and multi-drug resistant bacteria are causing outbreaks of potentially fatal diseases in hospitals and in the community.
Why Was This Study Done?
Although epidemiological studies (investigations of the causes, distribution, and control of disease in population) show a correlation between antibiotic use and antibiotic resistance in populations, such studies cannot prove that antibiotic use actually causes antibiotic resistance. It could be that the people who use more antibiotics share other characteristics that increase their chance of developing antibiotic resistance (so-called “confounding”). A causal link between antibiotic use and the development of antibiotic resistance can only be established by doing a randomized controlled trial. In such trials, groups of individuals are chosen at random to avoid confounding, given different treatments, and outcomes in the different groups compared. Here, the researchers undertake a randomized clinical trial to assess whether macrolide resistance is higher in communities treated with azithromycin for trachoma than in untreated communities. Azithromycin—an erythromycin derivative—is used to treat common bacterial infections such as middle ear infections caused by Streptococcus pneumoniae. Trachoma—the world's leading infectious cause of blindness—is caused by Chlamydia trachomatis. The World Health Organization's trachoma elimination strategy includes annual azithromycin treatment of at-risk communities.
What Did the Researchers Do and Find?
In this cluster-randomized trial (a study that randomly assigns groups of people rather than individuals to different treatments), 12 Ethiopian communities received mass azithromycin treatment of children aged 1–10 years old at 0, 3, 6, and 9 months, and 12 control communities received the antibiotic only at 12 months. The researchers took nasopharyngeal (nose and throat) swabs from randomly selected treated children at 0 and 12 months and from randomly selected control children at 12 months. They isolated S. pneumoniae from the swabs and tested the isolates for antibiotic susceptibility. 70%–80% of the children tested had S. pneumoniae in their nose or throat. In the treated group, 3.6% of monitored children were carrying azithromycin-resistant S. pneumoniae at 0 months, whereas 46.9% were doing so at 12 months—a statistically significant increase. Only 9.2% of the monitored children in the untreated group were carrying azithromycin-resistant S. pneumoniae at 12 months, a significantly lower prevalence than in the treated group. Importantly, there was no resistance to penicillin in any S. pneumoniae isolates obtained from the treated children at 0 or 12 months; one penicillin-resistant isolate was obtained from the control children.
What Do These Findings Mean?
These findings indicate that macrolide resistance is higher in nasopharyngeal S. pneumoniae in communities receiving intensive azithromycin treatment than in untreated communities. Thus, they support the idea that frequent antibiotic use selects for antibiotic resistance in populations. Although the study was undertaken in Ethiopian communities with high rates of nasopharyngeal S. pneumoniae carriage, this finding is likely to be generalizable to other settings. Importantly, these findings have no bearing on current trachoma control activities, which use less frequent antibiotic treatments and are less likely to select for azithromycin resistance. The lack of any increase in penicillin resistance, which is usually the first-line therapy for S. pneumoniae infections, is also reassuring. However, although these findings suggest that the benefits of mass azithromycin treatment for trachoma outweigh any potential adverse affects, they nonetheless highlight the importance of continued monitoring for the secondary effects of mass antibiotic distributions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000377.
The Bugs and Drugs website provides information about antibiotic resistance and links to other resources
The US National Institute of Allergy and Infectious Diseases provides information on antimicrobial drug resistance and on diseases caused by S. pneumoniae (pneumococcal diseases)
The US Centers for Disease Control and Prevention also have information on antibiotic resistance (in English and Spanish)
The World Health Organization has information about the global threat of antimicrobial resistance and about trachoma (in several languages)
More information about the trial described in this paper is available on ClinicalTrials.gov
doi:10.1371/journal.pmed.1000377
PMCID: PMC3001893  PMID: 21179434
18.  A ten year analysis of multi-drug resistant blood stream infections caused by Escherichia coli & Klebsiella pneumoniae in a tertiary care hospital 
Background & objectives:
Extensive use of antibiotics has added to the escalation of antibiotic resistance. This study was undertaken to evaluate the association, if any between antibiotic use and resistance in a hospital setting, and also detect the predominant mechanism of antibiotic resistance in Escherichia coli and Klebsiella pneumoniae over a period of 10 years.
Methods:
In a retrospective study of 10 years, a total of 77,618 blood culture samples from 2000 to 2009 from indoor patients were screened and those yielding E. coli and K. pneumoniae were included in the study. Antibiotic susceptibility records as well as the percentage of ESBL producers were noted. A total of 423 isolates of 2009 were also screened for AmpC and carbapenemase production. Antibiotic consumption data of 10 years were analysed.
Results:
ESBL producing E. coli increased from 40 per cent in 2002 to 61 per cent in 2009, similarly there was a significant (P<0.05) rise in resistance to cefotaxime (75 to 97%), piperacillin-tazobactum (55- 84%) and carbapenem (2.4-52%) in K. pneumoniae. A significant (P<0.05) association was observed between resistance and consumption of carbapenem and piperacillin and tazobactum consumption in K. pneumonia.
Interpretation & conclusions:
Our study demonstrated a rise in consumption and resistance to broad spectrum antimicrobial agents and also established an association between consumption and resistance to these antibiotics. Over a period of 10 years, the emergence of pan-resistance in K. pneumoniae could be due to the production of carbapenemases whereas ESBL production was the common mechanism of resistance in E. coli. This study warrants a directed effort towards continued surveillance and antibiotic stewardship to minimize selection pressure and spread.
PMCID: PMC3410219  PMID: 22825611
Antibiotic resistance; blood stream infection; Escherichia coli; Klebsiella pneumoniae
19.  Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007 
PLoS Medicine  2009;6(6):e1000084.
Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children.
Background
Overuse of antibiotics is the main force driving the emergence and dissemination of bacterial resistance in the community. France consumes more antibiotics and has the highest rate of beta-lactam resistance in Streptococcus pneumoniae than any other European country. In 2001, the government initiated “Keep Antibiotics Working”; the program's main component was a campaign entitled “Les antibiotiques c'est pas automatique” (“Antibiotics are not automatic”) launched in 2002. We report the evaluation of this campaign by analyzing the evolution of outpatient antibiotic use in France 2000–2007, according to therapeutic class and geographic and age-group patterns.
Methods and Findings
This evaluation is based on 2000–2007 data, including 453,407,458 individual reimbursement data records and incidence of flu-like syndromes (FLSs). Data were obtained from the computerized French National Health Insurance database and provided by the French Sentinel Network. As compared to the preintervention period (2000–2002), the total number of antibiotic prescriptions per 100 inhabitants, adjusted for FLS frequency during the winter season, changed by −26.5% (95% confidence interval [CI] −33.5% to −19.6%) over 5 years. The decline occurred in all 22 regions of France and affected all antibiotic therapeutic classes except quinolones. The greatest decrease, −35.8% (95% CI −48.3% to −23.2%), was observed among young children aged 6–15 years. A significant change of −45% in the relationship between the incidence of flu-like syndromes and antibiotic prescriptions was observed.
Conclusions
The French national campaign was associated with a marked reduction of unnecessary antibiotic prescriptions, particularly in children. This study provides a useful method for assessing public-health strategies designed to reduce antibiotic use.
Editors' Summary
Background
In 1928, Alexander Fleming discovered penicillin, the first antibiotic (a drug that kills bacteria). By the early 1940s, large amounts of penicillin could be made and, in the following decades, several other classes of powerful antibiotics were discovered. For a time, it looked like bacteria and the diseases that they cause had been defeated. But bacteria rapidly became resistant to these wonder drugs and nowadays, antibiotic resistance is a pressing public-health concern. Almost every type of disease-causing bacteria has developed resistance to one or more antibiotic in clinical use, and multidrug-resistant bacteria are causing outbreaks of potentially fatal diseases in hospitals and in the community. For example, multidrug-resistant Streptococcus pneumoniae (multidrug-resistant pneumococci or MRP) is now very common. S. pneumoniae colonize the nose and throat (the upper respiratory tract) and can cause diseases that range from mild ear infections to life-threatening pneumonia, particularly in young children and elderly people.
Why Was This Study Done?
For years, doctors have been prescribing (and patients have been demanding) antibiotics for viral respiratory infections (VRIs) such as colds and flu even though antibiotics do not cure viral infections. This overuse of antibiotics has been the main driving force in the spread of MRP. Thus, the highest rate of S. pneumoniae antibiotic resistance in Europe occurs in France, which has one of the highest rates of antibiotic consumption in the world. In 2001 France initiated “le plan national pour préserver l'efficacité des antibiotiques” to reduce the inappropriate use of antibiotics, particularly for the treatment of VRIs among children. The main component of the program was the “Antibiotiques c'est pas automatique” (“Antibiotics are not automatic”) campaign, which ran from 2002 to 2007 during the winter months when VRIs mainly occur. The campaign included an educational campaign for health care workers, the promotion of rapid tests for diagnosis of streptococcal infections, and a public information campaign about VRIs and about antibiotic resistance. In this study, the researchers evaluate the campaign by analyzing outpatient antibiotic use throughout France from 2000 to 2007.
What Did the Researchers Do and Find?
The researchers obtained information about antibiotic prescriptions and about the occurrence of flu-like illnesses during the study period from the French National Health Insurance database and national disease surveillance system, respectively. After adjusting for variations in the frequency of flu-like illnesses, compared to the preintervention period (2000–2002), the number of antibiotic prescriptions per 100 inhabitants decreased by a quarter over the five winters of the “Antibiotics are not automatic” campaign. The use of all major antibiotic classes except quinolones decreased in all 22 regions of France. Thus, whereas in 2000, more than 70 prescriptions per 100 inhabitants were issued during the winter in 15 regions, by 2006/7, no regions exceeded this prescription rate. The greatest decrease in prescription rate (a decrease of more than a third by 2006/7) was among children aged 6–15 years. Finally, although the rates of antibiotic prescriptions reflected the rates of flu-like illness throughout the campaign, by 2006/7 this relationship was much weaker, which suggests that fewer antibiotics were being prescribed for VRIs.
What Do These Findings Mean?
These findings indicate that the “Antibiotics are not automatic” campaign was associated with a reduction in antibiotic prescriptions, particularly in children. Because the whole French population was exposed to the campaign, these findings do not prove that the campaign actually caused the reduction in antibiotic prescriptions. The observed decrease might have been caused by other initiatives in France or elsewhere or by the introduction of a S. pneumoniae vaccine during the study period, for example. However, an independent survey indicated that fewer members of the public expected an antibiotic prescription for a VRI at the end of the campaign than at the start, that more people knew that antibiotics only kill bacteria, and that doctors were more confident about not prescribing antibiotics for VRIs. Thus, campaigns like “Antibiotics are not automatic” may be a promising way to reduce the overuse of antibiotics and to slow the spread of antibiotic resistance until new classes of effective antibiotics are developed.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000084.
This study is further discussed in a PLoS Medicine Perspective by Stephen Harbarth and Benedikt Huttner
The Bugs and Drugs Web site from the UK National electronic Library of Infection provides information about antibiotic resistance and links to other resources
The US National Institute of Allergy and Infectious Diseases provides information on antimicrobial drug resistance and on pneumococcal pneumonia
The US Centers for Disease Control and Prevention also have information on antibiotic resistance (in English and Spanish)
The European Surveillance of Antimicrobial Consumption Web site provides information on antibiotic consumption in European countries
Les antibiotiques c'est pas automatique provides information about the “Antibiotics are not automatic” campaign (in French)
Information on the Plan National pour Pérserver l'efficacité des antibiotiques is also available (in French)
doi:10.1371/journal.pmed.1000084
PMCID: PMC2683932  PMID: 19492093
20.  Discovery of a living coral reef in the coastal waters of Iraq 
Scientific Reports  2014;4:4250.
Until now, it has been well-established that coral complex in the Arabian/Persian Gulf only exist in the coastal regions of Bahrain, Iran, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates and it was thought that there are no coral reefs in Iraq. However, here for the first time we show the existence of a living 28 km2 large coral reef in this country. These corals are adapted to one of the most extreme coral-bearing environments on earth: the seawater temperature in this area ranges between 14 and 34°C. The discovery of the unique coral reef oasis in the turbid coastal waters of Iraq will stimulate the interest of governmental agencies, environmental organizations, as well as of the international scientific community working on the fundamental understanding of coral marine ecosystems and global climate today.
doi:10.1038/srep04250
PMCID: PMC3945051  PMID: 24603901
21.  Rationale, Design, Methodology and Hospital Characteristics of the First Gulf Acute Heart Failure Registry (Gulf CARE) 
Background:
There is paucity of data on heart failure (HF) in the Gulf Middle East. The present paper describes the rationale, design, methodology and hospital characteristics of the first Gulf acute heart failure registry (Gulf CARE).
Materials and Methods:
Gulf CARE is a prospective, multicenter, multinational registry of patients >18 year of age admitted with diagnosis of acute HF (AHF). The data collected included demographics, clinical characteristics, etiology, precipitating factors, management and outcomes of patients admitted with AHF. In addition, data about hospital readmission rates, procedures and mortality at 3 months and 1-year follow-up were recorded. Hospital characteristics and care provider details were collected. Data were entered in a dedicated website using an electronic case record form.
Results:
A total of 5005 consecutive patients were enrolled from February 14, 2012 to November 13, 2012. Forty-seven hospitals in 7 Gulf States (Oman, Saudi Arabia, Yemen, Kuwait, United Gulf Emirates, Qatar and Bahrain) participated in the project. The majority of hospitals were community hospitals (46%; 22/47) followed by non-University teaching (32%; 15/47 and University hospitals (17%). Most of the hospitals had intensive or coronary care unit facilities (93%; 44/47) with 59% (28/47) having catheterization laboratory facilities. However, only 29% (14/47) had a dedicated HF clinic facility. Most patients (71%) were cared for by a cardiologist.
Conclusions:
Gulf CARE is the first prospective registry of AHF in the Middle East, intending to provide a unique insight into the demographics, etiology, management and outcomes of AHF in the Middle East. HF management in the Middle East is predominantly provided by cardiologists. The data obtained from this registry will help the local clinicians to identify the deficiencies in HF management as well as provide a platform to implement evidence based preventive and treatment strategies to reduce the burden of HF in this region.
doi:10.4103/1995-705X.132137
PMCID: PMC4062990  PMID: 24949181
Acute heart failure; gulf; heart failure; middle east
22.  Daptomycin-Resistant Enterococcus faecalis Diverts the Antibiotic Molecule from the Division Septum and Remodels Cell Membrane Phospholipids 
mBio  2013;4(4):e00281-13.
ABSTRACT
Treatment of multidrug-resistant enterococci has become a challenging clinical problem in hospitals around the world due to the lack of reliable therapeutic options. Daptomycin (DAP), a cell membrane-targeting cationic antimicrobial lipopeptide, is the only antibiotic with in vitro bactericidal activity against vancomycin-resistant enterococci (VRE). However, the clinical use of DAP against VRE is threatened by emergence of resistance during therapy, but the mechanisms leading to DAP resistance are not fully understood. The mechanism of action of DAP involves interactions with the cell membrane in a calcium-dependent manner, mainly at the level of the bacterial septum. Previously, we demonstrated that development of DAP resistance in vancomycin-resistant Enterococcus faecalis is associated with mutations in genes encoding proteins with two main functions, (i) control of the cell envelope stress response to antibiotics and antimicrobial peptides (LiaFSR system) and (ii) cell membrane phospholipid metabolism (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase). In this work, we show that these VRE can resist DAP-elicited cell membrane damage by diverting the antibiotic away from its principal target (division septum) to other distinct cell membrane regions. DAP septal diversion by DAP-resistant E. faecalis is mediated by initial redistribution of cell membrane cardiolipin-rich microdomains associated with a single amino acid deletion within the transmembrane protein LiaF (a member of a three-component regulatory system [LiaFSR] involved in cell envelope homeostasis). Full expression of DAP resistance requires additional mutations in enzymes (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase) that alter cell membrane phospholipid content. Our findings describe a novel mechanism of bacterial resistance to cationic antimicrobial peptides.
IMPORTANCE  The emergence of antibiotic resistance in bacterial pathogens is a threat to public health. Understanding the mechanisms of resistance is of crucial importance to develop new strategies to combat multidrug-resistant microorganisms. Vancomycin-resistant enterococci (VRE) are one of the most recalcitrant hospital-associated pathogens against which new therapies are urgently needed. Daptomycin (DAP) is a calcium-decorated antimicrobial lipopeptide whose target is the bacterial cell membrane. A current paradigm suggests that Gram-positive bacteria become resistant to cationic antimicrobial peptides via an electrostatic repulsion of the antibiotic molecule from a more positively charged cell surface. In this work, we provide evidence that VRE use a novel strategy to avoid DAP-elicited killing. Instead of “repelling” the antibiotic from the cell surface, VRE diverts the antibiotic molecule from the septum and “traps” it in distinct membrane regions. We provide genetic and biochemical bases responsible for the mechanism of resistance and disclose new targets for potential antimicrobial development.
IMPORTANCE 
The emergence of antibiotic resistance in bacterial pathogens is a threat to public health. Understanding the mechanisms of resistance is of crucial importance to develop new strategies to combat multidrug-resistant microorganisms. Vancomycin-resistant enterococci (VRE) are one of the most recalcitrant hospital-associated pathogens against which new therapies are urgently needed. Daptomycin (DAP) is a calcium-decorated antimicrobial lipopeptide whose target is the bacterial cell membrane. A current paradigm suggests that Gram-positive bacteria become resistant to cationic antimicrobial peptides via an electrostatic repulsion of the antibiotic molecule from a more positively charged cell surface. In this work, we provide evidence that VRE use a novel strategy to avoid DAP-elicited killing. Instead of “repelling” the antibiotic from the cell surface, VRE diverts the antibiotic molecule from the septum and “traps” it in distinct membrane regions. We provide genetic and biochemical bases responsible for the mechanism of resistance and disclose new targets for potential antimicrobial development.
doi:10.1128/mBio.00281-13
PMCID: PMC3735187  PMID: 23882013
23.  Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis 
Objective
Bacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia.
Methods
This was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed.
Results
The most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n = 7, 71%–100%), other Klebsiella species (n = 7, 28%–80%), and Staphylococcus (n = 36, 25%–40%).
Conclusions
The common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high sensitivity to cephalosporins used in the empirical treatment of meningitis. The resistance of the common isolates to penicillin is high. Most ESBL K. pneumoniae were isolated from CSF samples drawn from neonates and were found to be resistant to the antibiotics recommended in the Namibia STGs. Based on the above findings, it is recommended to use a combination of aminoglycoside and third-generation cephalosporin to treat non–ESBL Klebsiella isolates. Carbapenems (e.g., meropenem) and piperacillin/tazobactam should be considered for treating severely ill patients with suspected ESBL Klebsiella infection. Namibia should have a national antimicrobial resistance surveillance system for early detection of antibiotics that may no longer be effective in treating meningitis and other life-threatening infections due to resistance.
doi:10.1186/2052-3211-6-4
PMCID: PMC3987067  PMID: 24764539
Celebrospinal fluid; Antimicrobial resistance; Culture and sensitivity; Empiric therapy; Meningitis; Namibia
24.  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.
doi:10.4103/0975-1483.80305
PMCID: PMC3122046  PMID: 21731362
Exports; Gulf cooperation council; pharmaceutical; regulatory
25.  Diarrhoeagenic Escherichia coli are not a significant cause of diarrhoea in hospitalised children in Kuwait 
BMC Microbiology  2009;9:62.
Background
The importance of diarrhoeagenic Escherichia coli (DEC) infections in the Arabian Gulf including Kuwait is not known. The prevalence of DEC (enterotoxigenic [ETEC], enteropathogenic [EPEC], enteroinvasive [EIEC], enterohemorrhagic [EHEC] and enteroaggregative [EAEC]) was studied in 537 children ≤ 5 years old hospitalised with acute diarrhoea and 113 matched controls from two hospitals during 2005–07 by PCR assays using E. coli colony pools.
Results
The prevalence of DEC varied from 0.75% for EHEC to 8.4% for EPEC (mostly atypical variety) in diarrhoeal children with no significant differences compared to that in control children (P values 0.15 to 1.00). Twenty-seven EPEC isolates studied mostly belonged to non-traditional serotypes and possessed β and θ intimin subtypes. A total of 54 DEC isolates from diarrhoeal children and 4 from controls studied for antimicrobial susceptibility showed resistance for older antimicrobials, ampicillin (0 to 100%), tetracycline (33 to 100%) and trimethoprim (22.2 to 100%); 43.1% of the isolates were multidrug-resistant (resistant to 3 or more agents). Six (10.4%) DEC isolates produced extended spectrum β-lactamases and possessed genetic elements (blaCTX-M, blaTEM and ISEcp1) associated with them.
Conclusion
We speculate that the lack of significant association of DEC with diarrhoea in children in Kuwait compared to countries surrounding the Arabian Gulf Region may be attributable to high environmental and food hygiene due to high disposable income in Kuwait.
doi:10.1186/1471-2180-9-62
PMCID: PMC2678128  PMID: 19331674

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