Antimicrobial resistance landscape and COVID-19 impact in Egypt, Iraq, Jordan, and Lebanon: A survey-based study and expert opinion.

OBJECTIVES: The objective of this study was to assess the antimicrobial resistance (AMR) landscape and the impact of COVID-19 on AMR in Egypt, Iraq, Jordan, and Lebanon, and to gather expert opinions on the barriers to the implementation of antimicrobial stewardship (AMS) initiatives in the region. METHODS: A cross-sectional questionnaire survey was used to assess the current AMR landscape, existing AMS initiatives, barriers to implementing AMS initiatives, and the impact of COVID-19 on AMR in the four countries. RESULTS: The survey was completed by 204 physicians from Egypt (n = 82), Lebanon (n = 49), Iraq (n = 43), and Jordan (n = 30). Previous antibiotic use and previous bacterial colonization were perceived as the most common risk factors for an increase in AMR. According to the survey, multidrug-resistant (MDR) gram-negative bacteria were most common in lower respiratory tract infections, and Klebsiella pneumoniae and Escherichia coli were the most commonly identified gram-negative bacteria in hospital-acquired infections. Only 14.8% of pediatric physicians and 28.6% of adult physicians reported that target pathogen genotyping and phenotyping were done in hospitals, and the most commonly reported reasons for the lack of testing were technological and resource constraints. These constraints, coupled with the scarcity and high cost of newer antibiotics, have been identified as the most significant barriers to the successful management of MDR gram-negative bacterial infections in the region. It was reported that the spectrum of activity and safety of the antibiotic, the site of infection, the presence of comorbidities, and published guidelines and local antibiograms determined the choice of empirical antibiotic therapy for patients in the region. The four countries experienced a significant rise in AMR due to several factors during the COVID-19 pandemic, including an increase in hospital occupancy, a shift in priorities away from AMR surveillance, and changes in AMR epidemiology. Additionally, the large volumes of unnecessary and unsubstantiated antibiotic prescriptions during the COVID-19 pandemic has led to subsequent antibiotic shortages and significant increases in AMR in the region. Physicians also noted that the majority of COVID-19 patients were already on antibiotics before visiting the healthcare facility. MDR gram-negative bacteria were found in the majority of COVID-19 patients admitted to the intensive care unit. Despite the fact that various AMS initiatives have been implemented, they are not standardized across the region. Some of the main barriers to AMS implementation in the region are a lack of adequately trained AMS staff, lack of AMS knowledge and training among healthcare professionals, financial constraints, and the lack of AMR surveillance systems. CONCLUSION: These survey results provide valuable insights into the existing AMR and AMS landscape in the region, as well as the barriers that impede efficient AMS and AMR management. Based on these findings, the authors developed a call to action that suggests ways for each country in the region to address these challenges.

A Narrative Review of Healthcare-Associated Gram-Negative Infections Among Pediatric Patients in Middle Eastern Countries.

INTRODUCTION: Gram-negative bacteria (GNB) have become prominent across healthcare and community settings due to factors including lack of effective infection control and prevention (ICP) and antimicrobial stewardship programs (ASPs), GNB developing antimicrobial resistance (AMR), and difficulty treating infections. This review summarizes available literature on healthcare-associated infections (HAIs) in Middle Eastern pediatric patients. METHODS: Literature searches were performed with PubMed and Embase databases. Articles not reporting data on GNB, HAIs, pediatric patients, and countries of interest were excluded. RESULTS: The searches resulted in 220 publications, of which 49 met the inclusion criteria and 1 additional study was identified manually. Among 19 studies across Egypt reporting GNB prevalence among pediatric patients, Klebsiella species/K. pneumoniae and Escherichia coli were typically the most common GNB infections; among studies reporting carbapenem resistance and multidrug resistance (MDR), rates reached 86% and 100%, respectively. Similarly, in Saudi Arabia, Klebsiella spp./K. pneumoniae and E. coli were the GNB most consistently associated with infections, and carbapenem resistance (up to 100%) and MDR (up to 75%) were frequently observed. In other Gulf Cooperation Council countries, including Kuwait, Oman, and Qatar, carbapenem resistance and MDR were also commonly reported. In Jordan and Lebanon, E. coli and Klebsiella spp./K. pneumoniae were the most common GNB isolates, and AMR rates reached 100%. DISCUSSION: This review indicated the prevalence of GNB-causing HAIs among pediatric patients in Middle Eastern countries, with studies varying in reporting GNB and AMR. Most publications reported antimicrobial susceptibility of isolated GNB strains, with high prevalence of extended-spectrum beta-lactamase-producing K. pneumoniae and E. coli isolates. A review of ASPs highlighted the lack of data available in the region. CONCLUSIONS: Enhanced implementation of ICP, ASPs, and AMR surveillance is necessary to better understand the widespread burden of antimicrobial-resistant GNB and to better manage GNB-associated HAIs across Middle Eastern countries.

Phenotypic and genotypic characterisation of cephalosporin-, carbapenem- and colistin-resistant Gram-negative bacterial pathogens in Lebanon, Jordan and Iraq.

Antimicrobial resistance (AMR) is a worldwide health concern that continues to escalate. A PubMed literature search identified articles from January 2015-August 2020 reviewing cephalosporin-, carbapenem- and colistin-resistant Gram-negative bacteria (GNB) in Lebanon, Jordan and Iraq, specifically focused on three main pathogens, namely Acinetobacter spp., Enterobacteriaceae (i.e. Escherichia coli and Klebsiella spp.) and Pseudomonas aeruginosa. Sixty-seven relevant articles published within the past 5 years highlighting trends in AMR in Lebanon, Jordan and Iraq were included. Increased resistance to carbapenems in Acinetobacter spp. isolates was observed in Lebanon, Jordan and Iraq; colistin resistance remained relatively low. Studies on Enterobacteriaceae isolates were more varied, with high rates of carbapenem and cephalosporin resistance and lower levels of colistin resistance in Lebanon. Studies from Iraq found high cephalosporin and colistin resistance along with increased susceptibility to carbapenems. In Jordan, most studies recorded high resistance to cephalosporins along with high susceptibility to carbapenems and colistin. Studies on P. aeruginosa isolates were limited: most isolates in Lebanon were carbapenem-resistant and colistin-susceptible; studies in Iraq showed varying levels of resistance to carbapenems and cephalosporins with high susceptibility to colistin; and studies in Jordan found varying levels of susceptibility to carbapenems, cephalosporins and colistin. The most commonly observed resistance mechanisms in GNB were genetic modifications causing increased expression of antimicrobial-inactivating enzymes and decreased permeability. Overall, this review highlights the concerning rise in AMR and the need for improved understanding of the resistance mechanisms to better inform healthcare providers when recommending treatment for patients in this region.

What would it take to eliminate tuberculosis in the Eastern Mediterranean Region? (Editorial).

Twenty-five years ago, tuberculosis (TB) was declared a global health emergency by the World Health Organization (WHO). However, TB still remained one of the top 10 causes of death worldwide in 2015. In 2014, the World Health Assembly (WHA) had approved a new global strategy to end TB that builds on successes achieved by the DOTS and the Stop TB Strategy. The End TB Strategy 2016-2035 envisions a world free of TB by pursuing policies that promote prevention and care, and encourage research and innovation, which is in line with the Sustainable Development Goals (SDGs) calling for the TB epidemic to end by 2030. In 2002, the Global Fund to fight AIDS, Tuberculosis and Malaria - a partnership between governments, civil society, private sector and patients - was launched to raise significant funds to support programmes in countries and communities most in need.

The role of antiepileptic drugs in free radicals generation and antioxidant levels in epileptic patients.

Many risk factors are encountered during the pathogenesis of epilepsy. In this study, the effect of seizure frequency on free radical generation and antioxidants levels in epileptic patients was evaluated. This study was carried out on 15 healthy controls (GI) and 60 epileptic patients treated with mono- or poly-therapy of carbamazepine, valproic acid, or phenytoin. The treated epileptic patients were divided into 2 main groups according to the seizure frequency: controlled seizure patients GII (n = 30) and uncontrolled seizure patients GIII (n = 30). GII included the GIIA subgroup (n = 15) which had been seizure free for more than 12 months and the GIIB subgroup (n = 15) which had been seizure free for a period from 6 to12 months. GIII included GIIIA (n = 15) and GIIIB (n = 15) for patients which had a seizure frequency of less than and more than four times/month, respectively. In comparison to the control group (GI), the levels of nitric oxide (NO) and malondialdehyde/creatinine ratio were significantly increased in GIIB, GIIIA, and GIIIB, while vitamins A and E levels were significantly decreased in GIIIB. Serum NO levels had significant negative correlations with serum vitamin E in the GIIA and GIIB groups, and with vitamin A in the GIIIA and GIIIB groups. However, serum NO had positive correlation with urinary MDA/Cr ratio. The imbalance between free radical generation and antioxidant system in epileptic patients may be a factor in seizure frequency.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.

Rapid identification of Pseudomonas aeruginosa by pulsed-field gel electrophoresis.

Twenty clinical Pseudomonas aeruginosa isolates recovered from patients admitted to The General Hospital in Ismailia Governorate (Egypt) were examined in this study. We analysed P. aeruginosa ATCC 9027 (as a control strain) and 19 of the isolates after digestion with SpeI restriction endonuclease. After this we conducted a pulsed-field gel electrophoresis (PFGE) and typed the obtained 10 unique patterns, designated as A, A1, B, B1, C, C1, D, D1, E and F. We evaluated the genetic relatedness between all strains, based on ≥87% band identity. As a result, the isolates were grouped in the 10 clusters as follows: patterns A, A1, B, B1, C contained two strains each and patterns C1, D, D1, E contained a single strain each; the five remaining strains were closely related (genomic pattern F). One isolate belonged to antibiotype 'b'. The genotype patterns of the P. aeruginosa ATCC 9027 control strain and isolate no. 11 were closely related and had two different antibiotypes 'd' and 'c', respectively.

The Global Fund's resource allocation decisions for HIV programmes: addressing those in need.

BACKGROUND: Between 2002 and 2010, the Global Fund to Fight AIDS, Tuberculosis and Malaria's investment in HIV increased substantially to reach US$12 billion. We assessed how the Global Fund's investments in HIV programmes were targeted to key populations in relation to disease burden and national income. METHODS: We conducted an assessment of the funding approved by the Global Fund Board for HIV programmes in Rounds 1-10 (2002-2010) in 145 countries. We used the UNAIDS National AIDS Spending Assessment framework to analyze the Global Fund investments in HIV programmes by HIV spending category and type of epidemic. We examined funding per capita and its likely predictors (HIV adult prevalence, HIV prevalence in most-at-risk populations and gross national income per capita) using stepwise backward regression analysis. RESULTS: About 52% ($6.1 billion) of the cumulative Global Fund HIV funding was targeted to low- and low-middle-income countries. Around 56% of the total ($6.6 billion) was channelled to countries in sub-Saharan Africa. The majority of funds were for HIV treatment (36%; $4.3 billion) and prevention (29%; $3.5 billion), followed by health systems and community systems strengthening and programme management (22%; $2.6 billion), enabling environment (7%; $0.9 billion) and other activities. The Global Fund investment by country was positively correlated with national adult HIV prevalence. About 10% ($0.4 billion) of the cumulative HIV resources for prevention targeted most-at-risk populations. CONCLUSIONS: There has been a sustained scale up of the Global Fund's HIV support. Funding has targeted the countries and populations with higher HIV burden and lower income. Prevention in most-at-risk populations is not adequately prioritized in most of the recipient countries. The Global Fund Board has recently modified eligibility and prioritization criteria to better target most-at-risk populations in Round 10 and beyond. More guidance is being provided for Round 11 to strategically focus demand for Global Fund financing in the present resource-constrained environment.

Romanian anti-TB drugs resistance surveillance 2003-2004.

UNLABELLED: Romania decided and initiated a DRS for anti-TB drugs at national level using the standardized methodology proposed by WHO and IUATLD. The DRS protocol was designed with technical assistance from WHO; the surveillance started in June 2003 and ended in June 2004. It was tested the susceptibility to the 4 first line anti-TB drugs: Isoniazide (H), Rifampicin (R), Streptomycin (S), Ethambutol (E). Drug susceptibility testing used: indirect absolute concentration method. There were included in the survey 1251 TB patients from the 60 clusters: 869 new cases and 382 previously treated. From the penitentiary system were included 85 TB patients, 47 new cases and 38 previously treated. RESULTS: [table: see text]. Estimations of the trend of anti-TB drug resistance in Romania for the next period was proposed.

Epidemiology of antituberculosis drug resistance (the Global Project on Anti-tuberculosis Drug Resistance Surveillance): an updated analysis.

BACKGROUND: The burden of tuberculosis is compounded by drug-resistant forms of the disease. This study aimed to analyse data on antituberculosis drug resistance gathered by the WHO and International Union Against Tuberculosis and Lung Disease Global Project on Anti-tuberculosis Drug Resistance Surveillance. METHODS: Data on drug susceptibility testing for four antituberculosis drugs--isoniazid, rifampicin, ethambutol, and streptomycin--were gathered in the third round of the Global Project (1999-2002) from surveys or ongoing surveillance in 79 countries or geographical settings. These data were combined with those from the first two rounds of the project and analyses were done. Countries that participated followed a standardised set of guidelines to ensure comparability both between and within countries. FINDINGS: The median prevalence of resistance to any of the four antituberculosis drugs in new cases of tuberculosis identified in 76 countries or geographical settings was 10.2% (range 0.0-57.1). The median prevalence of multidrug resistance in new cases was 1.0% (range 0.0-14.2). Kazakhstan, Tomsk Oblast (Russia), Karakalpakstan (Uzbekistan), Estonia, Israel, the Chinese provinces Liaoning and Henan, Lithuania, and Latvia reported prevalence of multidrug resistance above 6.5%. Trend analysis showed a significant increase in the prevalence of multidrug resistance in new cases in Tomsk Oblast (p<0.0001). Hong Kong (p=0.01) and the USA (p=0.0002) reported significant decreasing trends in multidrug resistance in new cases of tuberculosis. INTERPRETATION: Multidrug resistance represents a serious challenge for tuberculosis control in countries of the former Soviet Union and in some provinces of China. Gaps in coverage of the Global Project are substantial, and baseline information is urgently required from several countries with high tuberculosis burden to develop appropriate control interventions.

Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review.

In low-income and middle-income countries, direct (unconcentrated) sputum smear microscopy is the primary method for diagnosing pulmonary tuberculosis. The method is fast, inexpensive, and specific for Mycobacterium tuberculosis in high incidence areas. The main limitations of direct microscopy are its relatively low sensitivity, especially in individuals co-infected with HIV, and variable quality of the test in programme conditions. Thus, there is a need to identify methods to improve the sensitivity of microscopy. Physical and chemical sputum processing methods, including centrifugation, sedimentation, and bleach, have been studied and found to show promise. We did a systematic review to assess the ability of different processing methods to improve the sensitivity of microscopy. By searching many sources, we identified 83 studies. Overall, by comparison with direct smears, the results suggested that centrifugation with any of several chemical methods (including bleach) is more sensitive, that overnight sedimentation preceded by chemical processing is more sensitive, and that specificity is similar. There were insufficient data to determine the value of sputum processing methods in patients with HIV infection. Operational studies are needed to determine whether the increased sensitivity provided by processing methods is sufficient to offset their increased cost, complexity, and potential biohazards, and to examine their feasibility.

Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review.

Most of the world's tuberculosis cases occur in low-income and middle-income countries, where sputum microscopy with a conventional light microscope is the primary method for diagnosing pulmonary tuberculosis. A major shortcoming of conventional microscopy is its relatively low sensitivity compared with culture, especially in patients co-infected with HIV. In high-income countries, fluorescence microscopy rather than conventional microscopy is the standard diagnostic method. Fluorescence microscopy is credited with increased sensitivity and lower work effort, but there is concern that specificity may be lower. We did a systematic review to summarise the accuracy of fluorescence microscopy compared with conventional microscopy. By searching many databases and contacting experts, we identified 45 relevant studies. Sensitivity, specificity, and incremental yield were the outcomes of interest. The results suggest that, overall, fluorescence microscopy is more sensitive than conventional microscopy, and has similar specificity. There is insufficient evidence to determine the value of fluorescence microscopy in HIV-infected individuals. The results of this review provide a point of reference, quantifying the potential benefit of fluorescence microscopy, with which the increased cost and technical complexity of the method can be compared to determine the possible value of the method under programme conditions.

The World Health Organization/International Union Against Tuberculosis and Lung Disease Global Project on Surveillance for Anti-Tuberculosis Drug Resistance: a model for other infectious diseases.

Tuberculosis remains a global epidemic, with one-third of the population infected and 9 million active cases. Mono- and multidrug resistance in 6 World Health Organization (WHO) regions have been assessed in 40% of the global cases diagnosed by positive results of sputum testing. The 2004 report of the WHO Global Project on Anti-Tuberculosis Drug Resistance Surveillance confirms earlier findings that drug-resistant tuberculosis is ubiquitous and that multidrug-resistant tuberculosis has increased alarmingly. Control of tuberculosis, which is undermined by the human immunodeficiency virus (HIV) epidemic, is seriously jeopardized by multidrug resistant strains, for which treatment is complex, more costly, and less successful. Challenges for high-burden countries include implementation of the DOTS strategy and management of identified multidrug resistance with DOTS-Plus. Strengthening of the laboratory network in conjunction with improvement of surveillance, elucidation of the impact of HIV on transmission of tuberculosis and on amplification of resistance at individual and population levels, and implementation of private sector policies on drug resistance are imperative. New diagnostic tools and drugs are needed to expedite early detection and cure of multiresistant strains.

Guidelines for surveillance of drug resistance in tuberculosis

It defines resistance, and presents information on laboratories and diagnostic centres, sample size and sampling strategies, organization and survey outline, intake of patient, national reference laboratory, and data management and analysis. Publication from 2003, second edition. Document in pdf format.