Epidemiology of Reportable Bacterial Infectious Diseases in Saudi Arabia.

INTRODUCTION: Bacterial infections have a significant impact on human health; they can cause severe morbidity and mortality, particularly in susceptible populations. Epidemiological surveillance is a critical tool for monitoring the population's health and facilitate the prevention and control of infectious disease outbreaks. Knowing the burden of bacterial communicable diseases is an initial core step toward public health goals. METHODS: Saudi epidemiology surveillance data were utilized to depict the changing epidemiology of bacterial infectious diseases in Saudi Arabia from 2018 to 2021. The cumulative numbers of cases, demographics, and incidence rates were analyzed and visualized. Parametric tests were used to compare the difference in the mean values between categorical variables. Regression analysis was employed to estimate trends in disease rates over time. Statistical significance was set at p value ≤ 0.05. RESULTS: The results revealed that brucellosis, tuberculosis, and salmonellosis were the most frequently reported bacterial infectious diseases in Saudi Arabia. Males were more significantly affected by brucellosis and tuberculosis infections than females. Salmonellosis infections were more significant among Saudi citizens, while pulmonary tuberculosis was more significant in non-Saudis. Interestingly, there was a decline in the incidence rates of numerous bacterial infectious diseases during the Coronavirus Disease 2019 (COVID-19) pandemic and COVID-19 restrictions. Some bacterial infectious diseases were rarely reported in Saudi Arabia, including syphilis and diphtheria. CONCLUSIONS: The future perspective of this research is to enhance disease surveillance reporting by including different variables, such as the source of infection, travel history, hospitalization, and mortality rates. The aim is to improve the sensitivity and specificity of surveillance data and focus on the mortality associated with bacterial pathogens to identify the most significant threats and set a public health priority.

Localizing pharmaceuticals manufacturing and its impact on drug security in Saudi Arabia.

Local production of pharmaceuticals plays a vital role in maintaining resilience of national healthcare systems, especially when it comes to facilitating access to needed medicines and decreasing exposure to imports and international supply chains. Pharma is a research-intensive industry and the systemic lack of governance and support to R&D activities in this sector, among other host of related issues such as unsupportive regulatory regimes and human resources capacity limitations, is one of the major impediments to the diversifying of locally produced pharmaceuticals portfolio. In this review, an overview of the current pharmaceutical production system in Saudi Arabia, its major challenges, and proposed remedies to address them will be highlighted.

Optimization of amino acid-stabilized erythropoietin parenteral formulation: In vitro and in vivo assessment.

The aim of this study was to optimize the formulation of erythropoietin (EPO) using amino acids instead of human serum albumin (HSA) and to evaluate its in vivo stability in order to avoid the risk of viral contamination and antigenicity. Different EPO formulations were developed in such a way as to allow studying the effects of amino acids and surfactants on the EPO stability profile. The main techniques applied for EPO analysis were ELISA, Bradford method, and SDS gel electrophoresis. The in vivo stability was evaluated in a Balb-c mouse animal model. The results showed that the presence of surfactant was very useful in preventing the initial adsorption of EPO on the walls of vials and in minimizing protein aggregation. Amino acid combinations, glycine with glutamic acid, provided maximum stability. Formulation F4 (containing glycine, glutamic acid and Tween 20) showed minimum aggregation and degradation and in vivo activity equivalent to commercially available HSA-stabilized EPO (Eprex®).

Extended-spectrum and metallo-beta-lactamases among ceftazidime-resistant Pseudomonas aeruginosa in Riyadh, Saudi Arabia.

We investigated the extended-spectrum (ESBLs) and metallo-beta-lactamases (MBLs) among Pseudomonas aeruginosa isolates in Saudi Arabia. Disc susceptibility testing was performed on 200 P. aeruginosa isolates collected during 2010 at the Armed Forces Hospital in Riyadh, with MIC testing and phenotypic screening for ESBLs and MBLs carried out on those found to be ceftazidime resistant. Genes for ESBLs and MBLs were sought by PCR. Thirty-nine (19.5%) P. aeruginosa isolates were ceftazidime resistant, mostly with considerable resistance to other antibiotics except colistin. Twenty-three of these 39 (59%) appeared ESBL positive and 16 (41%) had MBLs. bla(VEB), and bla(GES) genes were found in 20 (86.95%), and 5 (21.74%) of 23 ESBL-positive isolates, respectively whilst bla(VIM) was detected in all 16 MBL-producers. bla(OXA-10-like) often accompanied bla(VEB), bla(VIM) or bla(GES). Several isolates had similar antibiogram and ß-lactamase profiles, and may represent outbreaks; nevertheless, the collection was not dominated by any single clone. This dominance of acquired ceftazidime-inactivating beta-lactamases, often in combination is in contrast to the situation in Europe and the USA, where most ceftazidime resistance in P. aeruginosa is attributable to AmpC and efflux.

High prevalence of acquired quinolone-resistance genes among Enterobacteriaceae from Saudi Arabia with CTX-M-15 ß-lactamase.

We examined the prevalence of acquired quinolone resistance determinants among Enterobacteriaceae with extended-spectrum ß-lactamases (ESBLs) in Riyadh, Saudi Arabia. qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA genes were sought by polymerase chain reaction (PCR) in 160 nonduplicate, clinical Enterobacteriaceae with ESBLs from Prince Salman Hospital in Riyadh during 2009. MICs were determined for qnr- and aac(6')-Ib-cr-positive isolates. Mutations in gyrA and parC were determined for isolates with qnr. ESBL genes were characterized by PCR and sequencing. Among 99 ESBL-producing Escherichia coli, 73% were ciprofloxacin resistant, as were 74% of 61 ESBL-positive Klebsiella pneumoniae. The aac(6')-1b-cr gene was present in 76 ESBL producers, comprising 34 K. pneumoniae and 42 E. coli, whereas qnrA or qnrB genes were found in 21 isolates, all of them also harbouring aac(6')-1b-cr and bla(CTX-M-15), with the latter encoding what was considerably the dominant ESBL in the collection. The qnr-positive isolates harboured a variety of mutation in gyrA and parC but, even with aac(6')-1b-cr also present, high-level ciprofloxacin resistance (MIC >32 µg/mL) was invariably associated with double mutations in gyrA, affecting both Ser83 and Asp87 along with >1 substitution in parC, affecting Ser80 or Glu84.

Novel erythropoietin-loaded nanoparticles with prolonged in vivo response.

The aim of this study was to incorporate human recombinant erythropoietin (EPO) in biodegradable polymeric nanoparticles targeting a prolonged-release effect. EPO-loaded poly(DL-lactide-co-glycolide) nanoparticles were prepared using double emulsion method (w/o/w) with least process-related stress on the encapsulated drug. The nanoparticles have been fully characterized including in vitro release profile. The biological activity was assessed in vivo using BALB-c mice. The produced particles appeared spherical in shape with smooth regular surfaces and had an average particle size of 225.9 ± 3.8 nm. The entrapment efficiency was 33.3%. The in vitro release profile exhibited a biphasic mode with a burst of 50% cumulative drug release, followed by a slow rate of release over 24 h, reaching a maximum of 82%. The bioassay results showed that EPO-loaded nanoparticles were able to maintain the physiological activity of EPO for 14 days after single subcutaneous injection compared with pure and marketed EPO formulae (EPREX®).

Distribution of Ambler class A, B and D ß-lactamases among Pseudomonas aeruginosa isolates.

OBJECTIVES: We determined the prevalence rate of classes A, B and D ß-lactamases among extended-spectrum cephalosporin (ESC)-non-susceptible Pseudomonas aeruginosa clinical isolates from burned patients. METHODS: Disc susceptibility testing was performed on 156 P. aeruginosa isolates collected during 2010 at Prince Salman Hospital in Riyadh, Saudi Arabia. Phenotypic screening of ESBLs and MBLs in the isolates resistant to ceftazidime (MIC>8 mg/L) was carried out. Genes encoding ESBLs and MBL were sought by PCR in ESBL- and MBL-producing isolates. RESULTS: The resistance rate to ceftazidime was 22.43%. The resistance rates for ESC-non-susceptible P. aeruginosa isolates to piperacillin, piperacillin/tazobactam, cefepime, aztreonam, imipenem, amikacin, gentamicin and ciprofloxacin were 100%, 71.14%, 88.57%, 48.57%, 70.0%, 82.5%, 87.5%, and 90.0% respectively. No resistance was detected to polymyxine B. The prevalence of ESBL and MBL in ESC-non-susceptible P. aeruginosa was 69.44% and 42.85%, respectively. The prevalence of structural genes for VEB-1, OXA-10 and GES ESBLs in P. aeruginosa was 68%, 56% and 20%, respectively. VIM gene was detected in 15 (100%) of MBL-producing isolates. OXA-10 like gene was concomitant with VEB, GES and/or VIM. Eight isolates harbored OXA-10 with VEB (imipenem MIC 6-8 mg/L), while five isolates harbored OXA-10 with VIM (imipenem MIC ≥ 32 mg/L) and one isolate contained OXA-10, VEB and GES (imipenem MIC 8 mg/L). PER was not detected in this study. CONCLUSION: VEB-1 and OXA-10 are the predominant ESBL genes and bla(VIM) is the dominate MBL gene in ESC-non-sensitive P. aeruginosa isolates in Saudi Arabia. VEB, OXA-10 and GES ESBLs have not been reported previously in Saudi Arabia and GES has not been reported previously in Middle East and North Africa.

Prevalence and genetic characteristics of TEM, SHV, and CTX-M in clinical Klebsiella pneumoniae isolates from Saudi Arabia.

The prevalence and genetic basis of extended-spectrum beta-lactamases (ESBLs) in Klebsiella pneumoniae remains unclear in Saudi Arabia. Therefore, this study was devoted to determine the prevalence and characterize ESBL-producing K. pneumoniae in Al-Qassim area, Saudi Arabia. A total of 430 isolates of K. pneumoniae isolated from clinical samples were collected over 6 months from January to June 2008. These isolates were screened for the presence of ESBLs by double-disk synergy test and re-evaluated by E-test ESBL method. Minimum inhibitory concentrations of 15 antibiotics against ESBL-positive strains were determined by E-test strips. The ß-lactamases involved were characterized by polymerase chain reaction assays and DNA sequencing. Conjugation experiments were done and ISEcp1 elements were tested among CTX-M positive isolates. The prevalence of ESBL was 25.6% (110/430) and all ESBL-positive isolates were sensitive to imipenem and tigecycline; however, the resistance rate to gentamicin, amikacin, and ciprofloxacin was 87.3%, 10%, and 9.1%, respectively. Of these, 89.1% produced SHV, 70.9% produced TEM, and 36.4% were CTX-M-producing strains. The prevalence of ESBL SHV SHV-12 and SHV-5 was of 60% and 18.2%, respectively, and various non-ESBL SHV, including SHV-1 (5.5%), -11 (3.6%), and -85 (1.8%), was detected. However, the prevalence of CTX-M-15 and CTX-M-14 was 34.5% and 1.8%, respectively. ISEcp1 element was detected in 60% of bla(CTX-M-15) genes. All bla(CTX-M) genes were transferable; however, most of bla(SHV-12) and bla(SHV-5) were not transferable. TEM-type ESBLs were not detected in any of the isolates. This is the first description of CTX-M-14, SHV-5, SHV-11, and SHV-85 in Saudi Arabia. We have documented the dominance of K. pneumoniae SHV-12 and highlighted the emergence of CTX-M-15 in Saudi Arabia.