Antimicrobial Resistance: A Growing Serious Threat for Global Public Health.

Antibiotics are among the most important discoveries of the 20th century, having saved millions of lives from infectious diseases. Microbes have developed acquired antimicrobial resistance (AMR) to many drugs due to high selection pressure from increasing use and misuse of antibiotics over the years. The transmission and acquisition of AMR occur primarily via a human-human interface both within and outside of healthcare facilities. A huge number of interdependent factors related to healthcare and agriculture govern the development of AMR through various drug-resistance mechanisms. The emergence and spread of AMR from the unrestricted use of antimicrobials in livestock feed has been a major contributing factor. The prevalence of antimicrobial-resistant bacteria has attained an incongruous level worldwide and threatens global public health as a silent pandemic, necessitating urgent intervention. Therapeutic options of infections caused by antimicrobial-resistant bacteria are limited, resulting in significant morbidity and mortality with high financial impact. The paucity in discovery and supply of new novel antimicrobials to treat life-threatening infections by resistant pathogens stands in sharp contrast to demand. Immediate interventions to contain AMR include surveillance and monitoring, minimizing over-the-counter antibiotics and antibiotics in food animals, access to quality and affordable medicines, vaccines and diagnostics, and enforcement of legislation. An orchestrated collaborative action within and between multiple national and international organizations is required urgently, otherwise, a postantibiotic era can be a more real possibility than an apocalyptic fantasy for the 21st century. This narrative review highlights on this basis, mechanisms and factors in microbial resistance, and key strategies to combat antimicrobial resistance.

Infective endocarditis: Role of molecular techniques in early diagnosis.

Infective endocarditis (IE), a heart valve infection primarily caused by bacteria such as streptococci or staphylococci, causes significant morbidity and mortality. Despite the long-term use of broad-spectrum antimicrobials, the infection is often difficult to manage. The latest diagnostic modalities for IE are discussed in this study. Blood culture use in pathogen identification can lead to loss of precious time as well as generation of false negative reports. The first steps in diagnosis are blood cultures and echocardiography, but molecular techniques can be extremely useful and may be used for an accurate and early diagnosis.

MERS-CoV: epidemiology, molecular dynamics, therapeutics, and future challenges.

The Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has gained research attention worldwide, given the current pandemic. Nevertheless, a previous zoonotic and highly pathogenic coronavirus, the Middle East Respiratory Syndrome coronavirus (MERS-CoV), is still causing concern, especially in Saudi Arabia and neighbour countries. The MERS-CoV has been reported from respiratory samples in more than 27 countries, and around 2500 cases have been reported with an approximate fatality rate of 35%. After its emergence in 2012 intermittent, sporadic cases, nosocomial infections and many community clusters of MERS continued to occur in many countries. Human-to-human transmission resulted in the large outbreaks in Saudi Arabia. The inherent genetic variability among various clads of the MERS-CoV might have probably paved the events of cross-species transmission along with changes in the inter-species and intra-species tropism. The current review is drafted using an extensive review of literature on various databases, selecting of publications irrespective of favouring or opposing, assessing the merit of study, the abstraction of data and analysing data. The genome of MERS-CoV contains around thirty thousand nucleotides having seven predicted open reading frames. Spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are the four main structural proteins. The surface located spike protein (S) of betacoronaviruses has been established to be one of the significant factors in their zoonotic transmission through virus-receptor recognition mediation and subsequent initiation of viral infection. Three regions in Saudi Arabia (KSA), Eastern Province, Riyadh and Makkah were affected severely. The epidemic progression had been the highest in 2014 in Makkah and Riyadh and Eastern Province in 2013. With a lurking epidemic scare, there is a crucial need for effective therapeutic and immunological remedies constructed on sound molecular investigations.

No association of the TGF-ß1 29T/C polymorphism with breast cancer risk in Caucasian and Asian populations: evidence from a meta-analysis involving 55,841 subjects.

The transforming growth factor-ß1 (TGF-ß1) gene 29 T/C polymorphism is thought to be associated with breast cancer risk. However, reports are largely conflicting and underpowered. We therefore conducted a meta- analysis of all available case-control studies relating the TGF-ß1 29T/C polymorphism to the risk of developing breast cancer by including a total of 31 articles involving 24,021 cases and 31,820 controls. Pooled ORs were generated for the allele contrasts, with additive genetic, dominant genetic and recessive genetic models. Subgroup analysis was also performed by ethnicity for the TGF-ß1 29T/C polymorphism. No association was found in the overall analysis (C vs T: OR=1.028, 95% CI=0.949-1.114, p-value 0.500; CC vs TC: OR=1.022, 95% CI=0.963- 1.085, p-value 0.478; CC vs TT: OR=1.054, 95% CI=0.898-1.236, p-value 0.522; CC vs TT+TC: OR=1.031, 95% CI=0.946-1.124, p-value 0.482; TT vs CC+TC: OR=0.945, 95% CI=0.827-1.080, p-value 0.403). Similarly, in the subgroup analysis by ethnicity, no association was found in Caucasian (C vs T: OR=1.041, 95% CI=0.932-1.162, p-value 0.475; CC vs TC: OR=1.031, 95% CI=0.951-1.118, p-value 0.464; CC vs TT: OR=1.081, 95% CI=0.865- 1.351, p-value 0.493; CC vs TT+TC: OR=1.047, 95% CI=0.929-1.180, p-value 0.453; TT vs CC+TC: OR= 0.929, 95% CI=0.775-1.114, p-value 0.429;) and Asian populations (C vs T: OR=1.004, 95% CI=0.908-1.111, p-value 0.931; CC vs TC: OR= 0.991, 95% CI=0.896-1.097, p-value 0.865; CC vs TT: OR=1.015, 95% CI=0.848-1.214, p-value 0.871; CC vs TT+TC: OR=1.000, 95% CI=0.909-1.101, p-value 0.994; TT vs CC+TC: OR= 0.967, 95% CI=0.808-1.159, p-value 0.720;). No evidence of publication bias was detected during the analysis. No significant association with breast cancer risk was demonstrated overall or on subgroup (Caucasian and Asian) analysis. It can be concluded that TGF-ß1 29T/C polymorphism does not play a role in breast cancer susceptibility in overall or ethnicity-specific manner.

Site-specific mouth rinsing can improve oral odor by altering bacterial counts. Blind crossover clinical study.

OBJECTIVES: To determine whether site-specific mouth rinsing with oral disinfectants can improve oral odor beyond the traditional panoral mouth disinfection with mouth rinses by targeting specifically oral malodor implicated anaerobic bacteria. METHODS: Twenty healthy fasting subjects volunteered for a blinded prospective, descriptive correlational crossover cross-section clinical trial conducted during the month of Ramadan between July and August 2013 in Albaha province in Saudi Arabia involving the application of Listerine Cool Mint mouth rinse by either the traditional panoral rinsing method, or a site-specific disinfection method targeting the subgingival and supragingival plaque and the posterior third of the tongue dorsum, while avoiding the remaining locations within the oral cavity. The viable anaerobic and aerobic bacterial counts, volatile sulfur compounds (VSCs) levels, organoleptic assessment of oral odor, and the tongue-coating index were compared at baseline, one, 5, and 9 hours after the treatment. RESULTS: The site-specific disinfection method reduced the VSCs and anaerobic bacterial loads while keeping the aerobic bacterial numbers higher than the traditional panoral rinsing method. CONCLUSION: Site-specific disinfection can more effectively maintain a healthy oral cavity by predominantly disinfecting the niches of anaerobic bacteria within the oral cavity.

Clostridium difficile in retail baskets, trolleys, conveyor belts, and plastic bags in Saudi Arabia.

OBJECTIVES: To determine Clostridium difficile (C. difficile) prevalence on retail surfaces and shoppers plastic bags. METHODS: From 20 June to 10 August 2011, in a cross-sectional epidemiological study, 17 supermarkets from 2 cities, Albaha and Altaif, Saudi Arabia were sampled. A total of 800 samples, which comprised 200 samples per surveyed surface, were studied. These included baskets, trolleys, conveyer belts, and outgoing shoppers' plastic bags. Clostridium difficile strains were isolated. The isolates were characterized using ribotyping and  polymerase chain reaction for the detection of toxin A (tcdA), toxin B (tcdB), binary toxin (cdtB), and toxin C (tcdC) genes. Susceptibility to antibiotics was determined on a Muller-Hinton agar with 5% sheep blood agar using E-tests. RESULTS: Overall, the C. difficile prevalence on sampled surfaces was 0.75%. The highest prevalence was found on retail baskets and trolleys, followed by plastic bags. A total of 5 different ribotypes were identified. Alterations in tcdC were detected in ribotype 027 and BT1. All the identified isolates were susceptible to vancomycin, but resistant to levofloxacin. CONCLUSION: In this study, C. difficile was present at a rate of 0.75% on supermarket surfaces. Spore disinfection of implicated surfaces may be necessary to control any community-acquired infections caused by this pathogen. 

No correlation between TIMP2 -418 G>C polymorphism and increased risk of cancer: evidence from a meta-analysis.

AIM: Tissue inhibitor of metalloproteinase (TIMP2) is involved in the regulation of matrix metalloproteinase 2 (MMP2) and shown to implicate in cancer development and progression. The results from the published studies based on the association between TIMP2 -418 G>C polymorphism and cancer risk are inconsistent. In this meta-analysis, we aimed to evaluate the potential association between TIMP2 -418 G>C polymorphism and cancer risk. METHODOLOGY: We searched PubMed (Medline) and EMBASE web databases to cover all studies based on relationship of TIMP2 -418 G>C polymorphism and risk of cancer until October 2013. The meta-analysis was performed for selected case-control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all genetic models. RESULTS: A total of 2225 cancer cases and 2532 controls were included from ten eligible case-control studies. Results from overall pooled analysis suggested no evidence of significant risk between TIMP2 -418 G>C polymorphism and cancer risk in any of the genetic models, such as, allele (C vs. G: OR = 1.293, 95% CI = 0.882 to 1.894, p = 0.188), homozygous (CC vs. GG: OR = 0.940, 95% CI = 0.434 to 2.039, p = 0.876), heterozygous (GC vs. GG: OR = 1.397, 95% CI = 0.888 to 2.198, p = 0.148), dominant (CC+GC vs. GG: OR = 1.387, 95% CI = 0.880 to 2.187, p = 0.159) and recessive (CC vs. GG+GC: OR = 0.901, 95% CI = 0.442 to 1.838, p = 0.774) models. No evidence of publication bias was detected during the analysis. CONCLUSIONS: The present meta-analysis suggests that the TIMP2 -418 G>C polymorphism may not be involved in predisposing risk factor for cancer in overall population. However, future larger studies with group of populations are needed to analyze the possible correlation.

Prevalence of mycobacteria in water reservoirs of Albaha, Saudi Arabia.

OBJECTIVE: To investigate for the presence of mycobacteria at water dams of Albaha, Saudi Arabia. METHODS: An epidemiological study was conducted between 20 - 30 June 2013 in the Albaha region, Kingdom of Saudi Arabia. Five hundred and twenty samples (sand, wet stones, clay, and decayed vegetation) were collected from 13 dams in the region. These locations were: 3 dams from Alaqiq city (Thrad, Alaqiq, and Almshereq); 4 dams from Almandaq city (Almudlamat, Alkhrar, Alsader, and Medhas); one dam from Albaha city (Shehba'a); and 5 dams from Baljerashi city (Alzarawah, Alareshaen, Almatwah, Alheajh, and Almarbah). Samples from these locations (n=520) were inoculated on Lowenstein-Jensen media. The isolated Mycobacterium (M.) obtained were identified by standard culture, enzymatic tests, biochemical characteristics, comparison of mycolic acid profiles, 16S rRNA gene sequencing, and restriction fragment patterns of the hsp65 gene polymerase chain reaction product. RESULTS: Mycobacterium isolates were recovered from 79% of the samples obtained from all types of samples and locations. A total of 145 of the isolates were found to belong to the 11 Mycobacterium species: 5 M. intracellulare, 8 M. abscessus, 9 M. szulgai, 12 M. fortuitum, 12 M. avium, 14 M. kansasii, 15 M. simiae, 15 M. gordonae, 16 M. terrae complex, 18 M. chelonae, and 21 M. malmoense. CONCLUSION: Mycobacterium species is present at high percentages in Albaha dams. The findings support a nationwide study to understand the clinical importance of environmental Mycobacterium in Saudi Arabia.

Evaluating the association between p53 codon 72 Arg>pro polymorphism and risk of ovary cancer: a meta-analysis.

AIM: Allelic polymorphism in codon 72 of the p53 tumor suppressor gene causes imbalance of p53 protein expression. Earlier studies have shown association between allelic polymorphism in codon 72 of the p53 gene with risk of ovary cancer (OC); however the results are inconclusive and conflicting. Therefore, we performed this meta-analysis to investigate the relation between p53 codon 72 Arg>Pro polymorphism and overall OC susceptibility. METHODS: We searched all eligible published studies based on the association between codon 72 of the p53 Arg>Pro polymorphism and risk of OC. Data were pooled together from individual studies and meta-analysis was performed. Pooled odds ratios (ORs) and 95% CI were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models. RESULTS: A total of twelve studies comprising of 993 OC cases and 1264 healthy controls were included in this meta-analysis. Overall, no significant association was detected for Pro allele carrier (Pro vs. Arg: p = 0.916; OR = 0.980, 95% CI = 0.677 to 1.419), homozygous (Pro/Pro vs. Arg/Arg: p = 0.419; OR = 0.731, 95% CI = 0.341 to 1.564), heterozygous (Arg/Pro vs. Arg/Arg: p = 0.248; OR = 1.237, 95% CI = 0.862 to 1.773), dominant (Pro/Pro+Arg/Pro vsArg/Arg: p = 0.699; OR = 1.089, 95% CI = 0.706 to 1.681), and recessive (Pro/Pro vs Arg/Arg+Arg/Pro: p = 0.329; OR = 0.754, 95% CI = 0.428 to 1.329) genetic models, respectively. Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of OC was found in the Caucasian population. CONCLUSIONS: This meta-analysis suggested that codon 72 of the p53 Arg>Pro polymorphism may not significantly contribute in ovary cancer susceptibility. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings.

Association between Papio hamadryas populations and human gastrointestinal infectious diseases in southwestern Saudi Arabia.

BACKGROUND AND OBJECTIVES: Papio hamadryas baboons, known reservoirs of several infectious diseases, roam and deposit their excreta indiscriminately on footpaths, parks, and streets of the city peripheries of Taif, Baha, and Abha in southwestern Saudi Arabia. Nonetheless, city centers of these places are free of baboons. This study aims to determine the impact of baboons on human gastrointestinal health. DESIGN AND SETTINGS: This is a descriptive cross-sectional analytical ecological study conducted in 3 cities located in southwestern Saudi Arabia between July 2011 and July 2012. MATERIALS AND METHODS: We investigated the impact of these baboons on the human health through a coprological survey of infectious agents of baboons and humans in these 3 cities using macroscopic and micro.scopic analyses, before and after parasite concentration, and culturing of bacteria on selective and differential media, which were then identified by 16S rDNA gene sequencing. Baboon fecal samples (n=823) were collected from city peripheries. Two groups of human fecal samples, each consisting of 795 samples were collected, one from city centers and the second from city peripheries where baboons intermingle with the human population. RESULTS: Baboon fecal samples were the most contaminated with infectious agents, except for Staphylococcus aureus, which was more commonly present in human fecal samples collected from city peripheries. Human fecal samples collected form city peripheries showed higher rates of most infective agents than those collected from city centers. CONCLUSION: This indicates that baboons are medically important reservoirs of infectious agents associated with higher human coproprevalence of gastrointestinal infectious agents.

A genetic association study of CCL5 -28 C>G (rs2280788) polymorphism with risk of tuberculosis: a meta-analysis.

AIM: The CC chemokine ligand 5 (CCL5), plays a key role in the inflammatory response by recruiting mononuclear cells during tuberculosis (TB) infection. Association studies of CCL5 -28 C>G (rs2280788) polymorphism and TB risk have shown inconsistent and contradictory results among different ethnic populations. The aim of this meta-analysis is to investigate the association between CCL5 -28 C>G polymorphism and TB susceptibility. METHODOLOGY: We performed quantitative synthesis for published studies based upon association between CCL5 -28 C>G polymorphism and TB risk from PubMed (Medline), EMBASE web databases. The meta-analysis was performed and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all genetic models. RESULTS: A total of six studies including 1324 TB cases and 1407 controls were involved in this meta-analysis. Variant allele (G vs. C: p = 0.257; OR = 1.809, 95% CI = 0.649 to 5.043), heterozygous (CG vs. CC: p = 0.443; OR = 1.440, 95% CI = 0.567 to 3.658) and homozygous (GG vs. CC: p = 0.160; OR = 5.140, 95% CI = 0.524 to 50.404) carriers did not show increased risk compare with those individual with the CC genotype. Similarly, no associations were found in the dominant (GG+CG vs. CC: p = 0.295; OR = 1.802, 95% CI = 0.599 to 5.412) and recessive (GG vs. CC+CG: p = 0.188; OR = 3.533, 95% CI = 0.541 to 23.085) models. CONCLUSIONS: Overall findings of this meta-analysis suggest that genetic polymorphism -28 C>G in CCL5 is not associated with increased TB risk. However, future larger studies with group of populations will be needed to analyze the relationship between the CCL5 -28 C>G polymorphism and risk of TB.

Quantitative determination by real-time PCR of four vaginal Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae indicates an inverse relationship between L. gasseri and L. iners.

BACKGROUND: Most studies of the vaginal microflora have been based on culture or on qualitative molecular techniques. Here we applied existing real-time PCR formats for Lactobacillus crispatus, L. gasseri and Gardnerella vaginalis and developed new formats for Atopobium vaginae, L. iners and L. jensenii to obtain a quantitative non culture-based determination of these species in 71 vaginal samples from 32 pregnant and 28 non-pregnant women aged between 18 and 45 years. RESULTS: The 71 vaginal microflora samples of these women were categorized, using the Ison and Hay criteria, as refined by Verhelst et al. (2005), as follows: grade Ia: 8 samples, grade Iab: 10, grade Ib: 13, grade I-like: 10, grade II: 11, grade III: 12 and grade IV: 7.L. crispatus was found in all but 5 samples and was the most frequent Lactobacillus species detected. A significantly lower concentration of L. crispatus was found in grades II (p < 0.0001) and III (p = 0.002) compared to grade I. L. jensenii was found in all grades but showed higher concentration in grade Iab than in grade Ia (p = 0.024). A. vaginae and G. vaginalis were present in high concentrations in grade III, with log10 median concentrations (log10 MC), respectively of 9.0 and 9.2 cells/ml. Twenty (38.5%) of the 52 G. vaginalis positive samples were also positive for A. vaginae. In grade II we found almost no L. iners (log10 MC: 0/ml) but a high concentration of L. gasseri (log10 MC: 8.7/ml). By contrast, in grade III we found a high concentration of L. iners (log10 MC: 8.3/ml) and a low concentration of L. gasseri (log10 MC: 0/ml). These results show a negative association between L. gasseri and L. iners (r = -0.397, p = 0.001) and between L. gasseri and A. vaginae (r = -0.408, p < 0.0001). CONCLUSION: In our study we found a clear negative association between L. iners and L. gasseri and between A. vaginae and L. gasseri. Our results do not provide support for the generally held proposition that grade II is an intermediate stage between grades I and III, because L. gasseri, abundant in grade II is not predominant in grade III, whereas L. iners, abundant in grade III is present only in low numbers in grade II samples.