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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.  Molecular Characterization of Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae in the Countries of the Gulf Cooperation Council: Dominance of OXA-48 and NDM Producers 
The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Enterobacteriaceae (CRE) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic-resistant genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Sixty-two isolates which screened positive for potential carbapenemase production were assessed, and 45 were found to produce carbapenemase. The most common carbapenemases were of the OXA-48 (35 isolates) and NDM (16 isolates) types; 6 isolates were found to coproduce the OXA-48 and NDM types. No KPC-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with seven clusters of clonally related Klebsiella pneumoniae. Awareness of CRE in GCC countries has important implications for controlling the spread of CRE in the Middle East and in hospitals accommodating patients transferred from the region.
doi:10.1128/AAC.02050-13
PMCID: PMC4068443  PMID: 24637692
3.  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
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.  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
6.  Medical education research in GCC countries 
Background
Medical education is an essential domain to produce physicians with high standards of medical knowledge, skills and professionalism in medical practice. This study aimed to investigate the research progress and prospects of GCC countries in medical education during the period 1996–2013.
Methods
In this study, the research papers published in various global scientific journals during the period 1996–2013 were accessed. We recorded the total number of research documents having an affiliation with GCC Countries including Saudi Arabia, Bahrain, Kuwait, Qatar, United Arab Emirates and Oman. The main source for information was Institute of Scientific Information (ISI) Web of Science, Thomson Reuters.
Results
In ISI-Web of Science, Saudi Arabia contributed 40797 research papers, Kuwait 1666, United Arab Emirates 3045, Qatar 4265, Bahrain 1666 and Oman 4848 research papers. However, in Medical Education only Saudi Arabia contributed 323 (0.79%) research papers, Kuwait 52 (0.03%), United Arab Emirates 41(0.01%), Qatar 37(0.008%), Bahrain 28 (0.06%) and Oman 22 (0.45%) research papers in in ISI indexed journals. In medical education the Hirsch index (h-index) of Saudi Arabia is 14, United Arab Emirates 14, Kuwait 11, Qatar 8, Bahrain 8 and Oman 5.
Conclusion
GCC countries produced very little research in medical education during the period 1996–2013. They must improve their research outcomes in medical education to produce better physicians to enhance the standards in medical practice in the region.
doi:10.1186/s12909-015-0293-6
PMCID: PMC4330984  PMID: 25638308
GCC; Medical Education; Research papers; Indexed Journal
7.  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
8.  Medical devices and the Middle East: market, regulation, and reimbursement in Gulf Cooperation Council states 
With some of the richest economies in the world, the Gulf Cooperation Council (GCC) is undergoing rapid growth not only in its population but also in health care expenditure. Despite the GCC’s abundance of hydrocarbon-based wealth, the drivers of the medical device industry in the GCC are still in flux, with gains yet to be made in areas of infrastructure, regulation, and reimbursement. However, the regional disease burden, expanding health insurance penetration, increasing privatization, and a desire to attract skilled expatriate health care providers have led to favorable conditions for the medical device market in the GCC. The purpose of this article is to investigate the current state of the GCC medical device industry, with respect to market, regulation, and reimbursement, paying special attention to the three largest medical device markets: Saudi Arabia, the United Arab Emirates, and Qatar. The GCC would seem to represent fertile ground for the development of medical technologies, especially those in line with the regional health priorities of the respective member states.
doi:10.2147/MDER.S73079
PMCID: PMC4242697  PMID: 25429243
medical devices; regulation; reimbursement; Middle East
9.  Financing healthcare in Gulf Cooperation Council countries: a focus on Saudi Arabia 
Background
This paper presents an analysis of the main characteristics of the Gulf Cooperation Council’s (GCC) health financing systems and draws similarities and differences between GCC countries and other high-income and low-income countries, in order to provide recommendations for healthcare policy makers. The paper also illustrates some financial implications of the recent implementation of the Compulsory Employment-based Health Insurance (CEBHI) system in Saudi Arabia.
Methods
Employing a descriptive framework for the country-level analysis of healthcare financing arrangements, we compared expenditure data on healthcare from GCC and other developing and developed countries, mostly using secondary data from the World Health Organization health expenditure database. The analysis was supported by a review of related literature.
Results
There are three significant characteristics affecting healthcare financing in GCC countries: (i) large expatriate populations relative to the national population, which leads GCC countries to use different strategies to control expatriate healthcare expenditure; (ii) substantial government revenue, with correspondingly high government expenditure on healthcare services in GCC countries; and (iii) underdeveloped healthcare systems, with some GCC countries’ healthcare indicators falling below those of upper-middle-income countries.
Conclusion
Reforming the mode of health financing is vital to achieving equitable and efficient healthcare services. Such reform could assist GCC countries in improving their healthcare indicators and bring about a reduction in out-of-pocket payments for healthcare.
doi:10.1002/hpm.2213
PMCID: PMC4260721  PMID: 23996348
financing healthcare; health insurance; Saudi health financing; GCC
10.  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
11.  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
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  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
20.  Evidence from the national health account: the case of Dubai 
Introduction
National health accounts (NHAs) provide useful information to aid in understanding the health care financing system. This article aims to present a profile of health system financing in Dubai using data from the NHA. We also aim to compare the provider structure of financing schemes in Dubai with those of the State of Qatar and selected Organization for Economic Cooperation and Development (OECD) countries.
Methods
The author analyzed secondary data published in NHAs for Dubai and Qatar, and data collected by the OECD countries and publicly available from the Statistical Office of the European Union (Eurostat), for 25 OECD countries for comparative analysis. All health financing measures used are as defined in the international System of Health Accounts (SHA).
Results
In Dubai, only 33% of current health expenditure (CHE) is funded by the government. However, the public sector is the main source of health funding in Qatar and most OECD countries, with an average of 79% and 72%, respectively. Households in Dubai spent about 22% of CHE, equivalent to an average US$187 per capita, ranking the highest among Gulf Cooperation Council (GCC) countries, and compared with 20% of CHE across OECD countries. Hospitals in Dubai accounted for 48% of CHE, which is much higher than Qatar (40%) and the OECD average (36%).
Conclusion
The Dubai health care financing system differs substantially from that in OECD countries, as it is more private oriented. The findings point to several potential opportunities for growth and improvement. Policy areas that may be addressed using the information presented in this article are broad and include the following: shift from hospital care to ambulatory and day care, sustainability of health finance, shift the cost of health care to the private sector, introduce cost-containment measures, revise payment systems for health providers, and produce subnational accounts for non-communicable diseases. More investment in the translation of national health account data into policy is suggested for future researchers.
doi:10.2147/RMHP.S69868
PMCID: PMC4181628  PMID: 25285027
Dubai; health finance; health account; health expenditures
21.  Correlations between Income Inequality and Antimicrobial Resistance 
PLoS ONE  2013;8(8):e73115.
Objectives
The aim of this study is to investigate if correlations exist between income inequality and antimicrobial resistance. This study’s hypothesis is that income inequality at the national level is positively correlated with antimicrobial resistance within developed countries.
Data collection and analysis
Income inequality data were obtained from the Standardized World Income Inequality Database. Antimicrobial resistance data were obtained from the European antimicrobial Resistance Surveillance Network and outpatient antimicrobial consumption data, measured by Defined daily Doses per 1000 inhabitants per day, from the European Surveillance of antimicrobial Consumption group. Spearman’s correlation coefficient (r) defined strengths of correlations of: > 0.8 as strong, > 0.5 as moderate and > 0.2 as weak. Confidence intervals and p values were defined for all r values. Correlations were calculated for the time period 2003-10, for 15 European countries.
Results
Income inequality and antimicrobial resistance correlations which were moderate or strong, with 95% confidence intervals > 0, included the following. Enterococcus faecalis resistance to aminopenicillins, vancomycin and high level gentamicin was moderately associated with income inequality (r= ≥0.54 for all three antimicrobials). Escherichia coli resistance to aminoglycosides, aminopenicillins, third generation cephalosporins and fluoroquinolones was moderately-strongly associated with income inequality (r= ≥0.7 for all four antimicrobials). Klebsiella pneumoniae resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones was moderately associated with income inequality (r= ≥0.5 for all three antimicrobials). Staphylococcus aureus methicillin resistance and income inequality were strongly associated (r=0.87).
Conclusion
As income inequality increases in European countries so do the rates of antimicrobial resistance for bacteria including E. faecalis, E. coli, K. pneumoniae and S. aureus. Further studies are needed to confirm these findings outside Europe and investigate the processes that could causally link income inequality and antimicrobial resistance.
doi:10.1371/journal.pone.0073115
PMCID: PMC3756954  PMID: 24009734
22.  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
23.  Presence of multi-drug resistant pathogenic Escherichia coli in the San Pedro River located in the State of Aguascalientes, Mexico 
Contamination of surface waters in developing countries is a great concern. Treated and untreated wastewaters have been discharged into rivers and streams, leading to possible waterborne infection outbreaks and may represent a significant dissemination mechanism of antibiotic resistance genes. In this study, the water quality of San Pedro River, the main river and pluvial collector of the Aguascalientes State, Mexico was assessed. Thirty sample locations were tested throughout the River. The main physicochemical parameters of water were evaluated. Results showed high levels of fecal pollution as well as inorganic and organic matter abundant enough to support the heterotrophic growth of microorganisms. These results indicate poor water quality in samples from different locations. One hundred and fifty Escherichia coli were collected and screened by PCR for several virulence genes. Isolates were classified as either pathogenic (n = 91) or commensal (n = 59). The disc diffusion method was used to determine antimicrobial susceptibility to 13 antibiotics. Fifty-two percent of the isolates were resistant to at least one antimicrobial agent and 30.6% were multi-resistant. Eighteen E. coli strains were quinolone resistant of which 16 were multi-resistant. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 12 isolates. Mutations at the Ser-83→Leu and/or Asp-87→Asn in the gyrA gene were detected as well as mutations at the Ser-80→Ile in parC. An E. coli microarray (Maxivirulence V 3.1) was used to characterize the virulence and antimicrobial resistance genes profiles of the fluoroquinolone-resistant isolates. Antimicrobial resistance genes such as blaTEM, sulI, sulII, dhfrIX, aph3 (strA), and tet (B) as well as integrons were found in fluoroquinolone (FQ) resistance E. coli strains. The presence of potential pathogenic E. coli and antibiotic resistance in San Pedro River such as FQ resistant E. coli could pose a potential threat to human and animal health.
doi:10.3389/fmicb.2013.00147
PMCID: PMC3683621  PMID: 23785356
water quality; antibiotic resistance; fluoroquinolone; virulence factors; pathogenic Escherichia coli
24.  Prevalence of antimicrobial resistance among bacterial pathogens isolated from cattle in different European countries: 2002–2004 
Background
The project "Antibiotic resistance in bacteria of animal origin – II" (ARBAO-II) was funded by the European Union (FAIR5-QLK2-2002-01146) for the period 2003–2005, with the aim to establish a continuous monitoring of antimicrobial susceptibility among veterinary laboratories in European countries based on validated and harmonised methodologies. Available summary data of the susceptibility testing of the bacterial pathogens from the different laboratories were collected.
Method
Antimicrobial susceptibility data for several bovine pathogens were obtained over a three year period (2002–2004). Each year the participating laboratories were requested to fill in excel-file templates with national summary data on the occurrence of antimicrobial resistance from different bacterial species.
A proficiency test (EQAS – external quality assurance system) for antimicrobial susceptibility testing was conducted each year to test the accuracy of antimicrobial susceptibility testing in the participating laboratories. The data from this testing demonstrated that for the species included in the EQAS the results are comparable between countries.
Results
Data from 25,241 isolates were collected from 13 European countries. For Staphylococcus aureus from bovine mastitis major differences were apparent in the occurrence of resistance between countries and between the different antimicrobial agents tested. The highest frequency of resistance was observed for penicillin. For Mannheimia haemolytica resistance to ampicillin, tetracycline and trimethoprim/sulphonamide were observed in France, the Netherlands and Portugal. All isolates of Pasteurella multocida isolated in Finland and most of those from Denmark, England (and Wales), Italy and Sweden were susceptible to the majority of the antimicrobials. Streptococcus dysgalactiae and Streptococcus uberis isolates from Sweden were fully susceptible. For the other countries some resistance was observed to tetracycline, gentamicin and erythromycin. More resistance and variation of the resistance levels between countries were observed for Escherichia coli compared to the other bacterial species investigated.
Conclusion
In general, isolates from Denmark, England (and Wales), the Netherlands, Norway, Sweden and Switzerland showed low frequencies of resistance, whereas many isolates from Belgium, France, Italy, Latvia and Spain were resistant to most antimicrobials tested. In the future, data on the prevalence of resistance should be used to develop guidelines for appropriate antimicrobial use in veterinary medicine.
doi:10.1186/1751-0147-50-28
PMCID: PMC2486267  PMID: 18611246
25.  Gram-Negative Infections in Adult Intensive Care Units of Latin America and the Caribbean 
This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs). A systematic search of the biomedical literature (PubMed) was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela) signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%). Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, accounted for >50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.
doi:10.1155/2014/480463
PMCID: PMC4265515  PMID: 25525515

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