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.

β-Lactamase production in key gram-negative pathogen isolates from the Arabian Peninsula.

The burden of antimicrobial resistance worldwide is substantial and is likely to grow. Many factors play a role in the emergence of resistance. These resistance mechanisms may be encoded on transferable genes, which facilitate the spread of resistance between bacterial strains of the same and/or different species. Other resistance mechanisms may be due to alterations in the chromosomal DNA which enables the bacteria to withstand the environment and multiply. Many, if not most, of the Gulf Corporation Council (GCC) countries do not have clear guidelines for antimicrobial use, and lack policies for restricting and auditing antimicrobial prescriptions. The aim of this study is to review the prevalence of antibiotic resistance in GCC countries and explore the reasons for antibiotic resistance in the region. The PubMed database was searched using the following key words: antimicrobial resistance, antibiotic stewardship, prevalence, epidemiology, mechanism of resistance, and GCC country (Saudi Arabia, Qatar, Bahrain, Kuwait, Oman, and United Arab Emirates). From January1990 through April 2011, there were 45 articles published reviewing antibiotic resistance in the GCC countries. Among all the GCC countries, 37,295 bacterial isolates were studied for antimicrobial resistance. The most prevalent microorganism was Escherichia coli (10,073/44%), followed by Klebsiella pneumoniae (4,709/20%), Pseudomonas aeruginosa (4,287/18.7%), MRSA (1,216/5.4%), Acinetobacter (1,061/5%), with C. difficile and Enterococcus representing less than 1%. In the last 2 decades, E. coli followed by Klebsiella pneumoniae were the most prevalent reported microorganisms by GCC countries with resistance data.

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The prevalence of antimicrobial resistance in clinical isolates from Gulf Corporation Council countries

Background: Over the past decade, the worldwide emergence of carbapenem resistance in Enterobacteriaceae has become a severe public health issue. This meta-analysis aims to describe the epidemiology of carbapenem resistant Enterobacteriaceae (CRE) during the years of 2000-2012 in Asian area. Methods: PubMed and Embase databases were searched to identify the qualified papers. Random or fixedeffect model was used to deal with the data. Results: Over all the 49 Asian countries (or regions), only 37.5% [19] of them contributed epidemiology data of CRE, and the rest ones provided either only case reports or no information at all. In Asia, the prevalence of CRE was still low during the study period with average resistance rates of 0.6% (95% CI, 0.6-0.8%, imipenem) and 0.9% (95% CI, 0.7-1.2%, meropenem). Resistance rates to imipenem and meropenem in Enterobacteriaceae exhibited stably escalating trend. Similar trend can also be observed among each Enterobacteriaceae genus, such as E. coli, Klebsiella spp. and Enterobacer spp. Klebsiella spp. accounted for the largest proportion among the isolates resistant to imipenem, and then followed by E. coli and Serratia. The rank order of resistance rates to imipenem among Enterobacteriaceae genus during the period of 2000-2012 was as follows: Serratia spp. (1.8%) > Proteus spp. (1.6%) > Klebsiella spp. (0.8%) = Citrobacter spp. (0.8%) > Enterobacer spp. (0.7%) > E. coli (0.2%). Conclusions: Given the fact that the prevalence of CRE was increasing during the past decade, it is urgent for us to establish regional surveillance worldwide, carry out more effective antibiotic stewardship and infection control measures to prevent further spread of carbapenem resistance in Enterobacteriaceae .

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Epidemiology of carbapenem resistant Enterobacteriaceae (CRE) during 2000-2012 in Asia

In the last decade, extended-spectrum cephalosporin and carbapenem resistant Gram-negative bacilli have been extensively reported in the literature as being disseminated in humans but also in animals and the environment. These resistant organisms often cause treatment challenges due to their wide spectrum of antibiotic resistance. With the emergence of colistin resistance in animals and its subsequent detection in humans, the situation was worsened. Several studies reported the transmission of resistant organisms from animals to humans. Studies from the middle east highlighted the spread of resistant organisms in hospitals and to a lesser extent in livestock and the environment. In view of the recent socio-economical conflicts that these countries are facing in addition to the constant population mobilization; we attempt in this review to highlight the gaps as for the prevalence of resistance, antibiotic consumption reports, infection control measures and other risk factors contributing in particular to the spread of resistance in these countries. In hospitals, carbapenemase producers appear to be dominant. In contrast, ESBLs and colistin resistance are becoming a serious problem in animals. This is mainly due to the continuous use of colistin in veterinary medicine although it was previously abandoned in the human sphere. In the environment, despite the small number of reports, ESBL and carbapenemase producers were both detected. This highlights the importance of this latter as a bridge between humans and animals in the transmission chain. In this review, we have noticed that in the majority of the Middle Eastern area, little is known about the level of antibiotic consumption especially in the community and animal farms. Furthermore, some countries are nowadays facing the burden of immigrants, poverty and poor living conditions imposed by the civil war crisis. This all facilitates more the dissemination of resistance in all environments. In the one health concept, this work re-emphasizes the need to have global intervention measures to avoid dissemination of antibiotic resistance in humans, animals and environment in Middle Eastern countries.

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Understanding the Epidemiology of Multi-Drug Resistant Gram-Negative Bacilli in the Middle East Using a One Health Approach.

The prevalence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-producing E coli) has recently increased worldwide This study aims at determining the antimicrobial susceptibility patterns of a collection of clinical E coli urine isolates and evaluating the ESBL carriage of these isolates at phenotypic and genotypic levels A total of 100 E coli urine isolates were collected at a tertiary healthcare centre in Riyadh from January 2018 to March 2018 Antimicrobial susceptibility testing was carried out for all isolates ESBL production was characterized at phenotypic and genotypic levels using double-disc synergy test and polymerase chain reaction, respectively Detection of different ESBL variants was performed using DNA sequencing Of 100 E coli isolates, 67 were associated with multidrug resistance (MDR) phenotype All isolates showed variable resistance levels to all antibiotics used here expect to imipenem, where they were all imipenem-sensitive 33 out of 100 E coli isolates were positive for ESBLs by phenotypic and genotypic methods Among all ESBL-positive E coli isolates, the CTX-M was the most prevalent ESBL type (31/33 isolates; 9394%) CTX-M-15 variant was detected in all isolates associated with CTX-M carriage Multiple ESBL gene carriage was detected in 15/33 isolates (4545%), where 11 (3333%) isolates produced two different ESBL types while 4 isolates (1212%) associated with carrying three different ESBL types Our study documented the high antimicrobial resistance of ESBL-producing E coli to many front-line antibiotics currently used to treat UTI patients, and this implies the need to continuously revise the local guidelines used for optimal empirical therapy for UTI patients It also showed the high prevalence of ESBL carriage in E coli urine isolates, with CTX-M-15 being the most predominant CTX-M variant

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Prevalence of Multidrug Resistance and Extended-Spectrum β-Lactamase Carriage of Clinical Uropathogenic Escherichia coli Isolates in Riyadh, Saudi Arabia

Self renewal and apoptosis of haemopoietic stem cells (HSC) represent major factors that determine the size of the haemopoietic cell mass. Changes in self renewal above or below the steady state value of 0.5 will result in either bone marrow expansion or aplasia, respectively. Despite the growing body of research that describes the potential role of HSC, there is still very little information on the mechanisms that govern HSC self renewal and apoptosis. Considerable insight into the role of HSC in many diseases has been gained in recent years. In light of their crucial importance, this article reviews recent developments in the understanding of the molecular, biological, and physiological characteristics of haemopoietic stem cells.

The haemopoietic stem cell: between apoptosis and self renewal.

The aim of this descriptive study was to determine the prevalence of Klebsiella pneumoniae from different clinical specimens, their antibiotic susceptibility pattern and the extended-spectrum β-lactamase (ESBL) production among such isolates at Armed Forces Hospital, Al-Kharaj, Saudi Arabia, from November, 2004 to October, 2007. A total of 328 isolates of K. pneumoniae recovered from 8152 different specimens were studied for ESBL production and antimicrobial susceptibility. The prevalence of K. pneumoniae was 4% (328/8152). We observed a high percentage of K. pneumoniae resistant to ampicillin (100%) and tetracycline (92%). The prevalence of ESBL-producing K. pneumoniae was found to be 10.4% (34/328). The ESBL-producing strains were mostly from aspirates (25%) followed by sputum (20%) and blood (18.2%). These ESBLproducing isolates were highly resistant to gentamicin and ciprofloxacin. All isolates were susceptible to imipenem. Our findings demonstrate a high percentage of ESBL-producers among clinical isolates of K. pneumoniae and a high rate of multidrug resistance. Continued infection control measures and prudent use of antimicrobial agents are essential in reducing the spread of multi-resistant ESBL-producing K. pneumoniae.

https://www.jcpsp.pk/archive/2009/Apr2009/18.pdf

Prevalence, antibiotic susceptibility pattern and production of extended-spectrum beta-lactamases amongst clinical isolates of Klebsiella pneumoniae at Armed Forces Hospital in Saudi Arabia.

Keywords: Antibiotic; Armed Forces Hospital; Methicillin resistant; Saudi Arabia; Staphylococcus aureus Online:Â 22 May 2009 DOI: 10.3329/bmrcb.v35i1.1983 Bangladesh Med Res Counc Bull 2009; 35: 28-30

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Prevalence and antibiotic susceptibility pattern of methicillin resistant Staphylococcus aureus at Armed Forces Hospital in Saudi Arabia.

Apoptosis plays a central role in the pathogenesis of a number of human diseases. Because apoptosis represents a fundamental process in the response to such infections, it may represent a therapeutic target for their treatment. There is thus likely to be future clinical relevance in harnessing our growing knowledge both of apoptotic mechanisms, and their regulation, in the search to achieve modalities for therapeutic benefit. This brief review aims to summarize what we currently know about the role of apoptosis in response to a range of microbial infections (including bacterial and viral).

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Role of Apoptosis in Microbial Infection

The replacement of diseased organs by transplantation is now an important medical therapy. However, transplantation is limited by organ shortage. One solution to this problem is xenotransplantation, in other words, the use of organs from animal donors. Although the problem of hyperacute rejection is now largely solved, there is evidence that xenografts suffer other forms of rejection, one of them being T cell response. Moreover, evidence suggests that the degree of immunosuppression required to prevent T cell mediated xenograft rejection will be higher than that needed to prevent T cell mediated allograft rejection. Thus, strategies for graft-specific immunosuppression and improved tolerance are needed, and are discussed in this review

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Shamweel Ahmad

Papers

The haemopoietic stem cell: between apoptosis and self renewal.

Prevalence, antibiotic susceptibility pattern and production of extended-spectrum beta-lactamases amongst clinical isolates of Klebsiella pneumoniae at Armed Forces Hospital in Saudi Arabia.

Prevalence and antibiotic susceptibility pattern of methicillin resistant Staphylococcus aureus at Armed Forces Hospital in Saudi Arabia.

Role of Apoptosis in Microbial Infection

Role of ctla-4 in xenotranplantation