Despite tremendous efforts to prevent central line-associated bloodstream infections, they still remain life-threatening complications among hospitalized patients with significant morbidity and ...mortality worldwide. The emerging antibiotic-resistant bacteria and other risk factors, including patient comorbidities, complicate patient management.
A single-center retrospective observational study was conducted at King Fahad Hospital of the University, Eastern Province, Saudi Arabia. Hospitalized patients with confirmed central line-associated bloodstream infections between January 2015 and December 2020 were included. The primary objectives were to investigate the trends in antibiotic susceptibility patterns of the causative agents, coexisting comorbid conditions, and other risk factors associated with mortality.
A total of 214 patients with confirmed central line-associated bloodstream infections were included (CLABSI). The overall 30-day mortality rate was 33.6%. The infection rates per 1000 central line days for medical, surgical, and pediatric intensive care units were 4.97, 2.99, and 4.56 per 1000 CL days, respectively. The overall microbiological trends showed a predominance of Gram-negative agents, a steady increase of fungal CLABSI up to 24.0% in 2020, and a high prevalence of multidrug resistance up to 47% of bacterial CLABSI. In addition, the study indicates a significant negative surviving correlation with diabetes mellitus, cardiovascular disease, lung disease, chronic kidney disease, and the presence of ≥ 3 comorbidities (P < 0.05).
The microbiological trends of the study population demonstrated a steady increase of CLABSI caused by Candida spp. with a predominance of Gram-negative pathogens. Stratifying the patients according to relevant mortality risk factors, including patient comorbidities, will help reduce CLABSI rates and improve patient outcomes.
Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in ...science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers’ interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.
The COVID-19 pandemic continues with new waves that could persist with the arrival of new SARS-CoV-2 variants. Therefore, the availability of validated and effective triage tools is the cornerstone ...for proper clinical management. Thus, this study aimed to assess the validity of the ISARIC-4C score as a triage tool for hospitalized COVID-19 patients in Saudi Arabia and to compare its performance with the CURB-65 score.
This retrospective observational cohort study was conducted between March 2020 and May 2021 at KFHU, Saudi Arabia, using 542 confirmed COVID-19 patient data on the variables relevant to the application of the ISARIC-4C mortality score and the CURB-65 score. Chi-square and t-tests were employed to study the significance of the CURB-65 score and the ISARIC-4C score variables considering the ICU requirements and the mortality of COVID-19 hospitalized patients. In addition, logistic regression was used to predict the variables related to COVID-19 mortality. In addition, the diagnostic accuracy of both scores was validated by calculating sensitivities, specificities, positive predictive value, negative predictive value, and Youden's J indices (YJI).
ROC analysis showed an AUC value of 0.834 95% CI; 0.800–0.865) for the CURB-65 score and 0.809 95% CI; 0.773–0.841) for the ISARIC-4C score. The sensitivity for CURB-65 and ISARIC-4C is 75% and 85.71%, respectively, while the specificity was 82.31% and 62.66%, respectively. The difference between AUCs was 0.025 (95% CI; −0.0203-0.0704, p = 0.2795).
Study results support external validation of the ISARIC-4C score in predicting the mortality risk of hospitalized COVID-19 patients in Saudi Arabia. In addition, the CURB-65 and ISARIC-4C scores showed comparable performance with good consistent discrimination and are suitable for clinical utility as triage tools for hospitalized COVID-19 patients.
Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are ...suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen’s favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.
Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is an important cause of sepsis in tropical areas of Eastern Asia, mainly affecting immunocompromised adults. Diabetes mellitus ...is the most important host risk factor. Here, we report a case of a 54-year-old Saudi male with uncontrolled diabetes mellitus for 10 years who presented to our hospital with a 6-week history of fever, cough, night sweats and weight loss. Definite diagnosis of melioidosis was not made because of insufficient facility to culture the organism in our laboratory; nevertheless, the diagnosis of melioidosis was made based on the cumulative clinical scenario. The patient was discharged with a prescription of trimethoprim-sulfamethoxazole and doxycycline for 3 months and showed dramatic improvement at follow-up. For prompt diagnosis and treatment, clinicians must maintain a high index of suspicion for melioidosis in febrile patients with a history of traveling to endemic areas, especially diabetic patients.
Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is an important cause of sepsis in tropical areas of Eastern Asia, mainly affecting immunocompromised adults. Diabetes mellitus is the most important host risk factor. Here, the authors report a case of a 54-year-old Saudi male with uncontrolled diabetes mellitus for 10 years who presented to our hospital with a 6-week history of fever, cough, night sweats and weight loss. The patient was a frequent traveler to the Philippines, with his last visit being during the rainy season 2 weeks before the onset of symptoms. Definite diagnosis of melioidosis was not made because of insufficient facility to culture the organism in our laboratory; nevertheless, a diagnosis of melioidosis was made based on the cumulative clinical scenario. The patient was discharged on trimethoprim-sulfamethoxazole and doxycycline for 3 months and showed significant improvement at follow-up. For prompt diagnosis and treatment, clinicians must maintain a high index of suspicion for melioidosis in febrile patients with a history of traveling to endemic areas, especially diabetic patients.
The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, ...increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs' phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.
Nasopharyngeal carcinoma (NPC) is an uncommon type of malignancy/cancer worldwide. However, NPC is an endemic disease in southeast Asia and southern China and the reasons behind the underlying for ...such changes are unclear. Even though the Epstein-Barr infection (EBV) has been suggested as an important reason for undistinguishable NPC, the EBV itself is not adequate to source this type of cancer. The risk factors, for example, genetic susceptibility, and environmental factors might be associated with EBV to undertake a part in the NPC carcinogenesis. Normal healthy people have a memory B cell pool where the EBV persists, and any disturbance of this connection leads to virus-associated B cell malignancies. Less is known about the relationship between EBV and epithelial cell tumors, especially the EBV-associated nasopharyngeal carcinoma (EBVaNPC) and EBV-associated gastric carcinoma (EBVaGC). Currently, it is believed that premalignant genetic changes in epithelial cells contribute to the aberrant establishment of viral latency in these tumors. The early and late phases of NPC patients' survival rates vary significantly. The presence of EBV in all tumor cells presents prospects for the development of innovative therapeutic and diagnostic techniques, despite the fact that the virus's exact involvement in the carcinogenic process is presently not very well known. EBV research continues to shed light on the carcinogenic process, which is important for a more comprehensive knowledge of tumor etiology and the development of targeted cancer therapeutics. In order to screen for NPC, EBV-related biomarkers have been widely used in a few high-incidence locations because of their close associations with the risks of NPC. The current review highlights the scientific importance of EBV and its possible association with NPC.
have been classified as severely drug resistant bacteria by the World Health Organization due to their extensive production and dissemination of carbapenemases (CPs) and extended-spectrum ...β-lactamases (ESBL). The current study was conducted with the aim to determine the prevalence of CP- and ESBL-producing
as well as their antibiotic susceptibility profiles. For this, a hospital-based study was conducted which included 384 participants with bacterial infections. The collection and processing of specimens was conducted per standard microbiological protocol. The samples were inoculated on agar media plates to obtain the bacterial growths, and if they were positive for any bacterial growth, the antibiotic susceptibility testing was performed using disk diffusion method to check their antibiotic susceptibility patterns. The double disc diffusion as well as carbapenem inhibition techniques were used to examine the CP enzymes. Multiplex real-time PCR technique was performed to identify three distinct genetic types of CPs that have been identified in the
(
,
, and
). A majority of participants (58.3%) in the current study were living in urban areas. A total of 227 (59.1%) patients were hospitalized. Furthermore, 26.04% of the patients were determined to be suffering from infections with
.
was the most prevalent (9.1%) isolate overall, followed by
(8.07%),
(2.6%),
(3.1%),
(1.3%),
spp. (1.3%), and
spp. (0.5%). The studied patients were suffering from urinary tract infections (48.6%), blood stream infections (32.2%), wounds infection (11.9%), and respiratory infections (7.03%), confirmed with bacterial cultures. The resistance against carbapenems was seen in 31.4% of
isolates, 25.8% in
, 50% in
, 25% in
, and 20% in
isolates. Such high rates of CP- and ESBL-producing
are alarming, suggesting high spread in the study area. It is advised to implement better infection prevention and control strategies and conduct further nationwide screening of the carriers of these pathogens. This might help in reducing the burden of highly resistant bugs.
The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, ...particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.
: The BaeR protein is involved in the adaptation system of
and is associated with virulence factors responsible for systemic infections in hospitalized patients. This study was conducted to ...characterize putative epitope peptides for the design of vaccines against BaeR protein, using an immune-informatic approach.
: FASTA sequences of BaeR from five different strains of
were retrieved from the UNIPROT database and evaluated for their antigenicity, allergenicity and vaccine properties using BepiPred, Vaxijen, AlgPred, AntigenPro and SolPro. Their physio-chemical properties were assessed using the Expasy Protparam server. Immuno-dominant B-cell and T-cell epitope peptides were predicted using the IEDB database and MHC cluster server with a final assessment of their interactions with TLR-2. Results: A final selection of two peptide sequences (36aa and 22aa) was made from the 38 antigenic peptides. E1 was considered a soluble, non-allergenic antigen, and possessed negative GRAVY values, substantiating the hydrophilic nature of the proteins. Further analysis on the T-cell epitopes, class I immunogenicity and HLA allele frequencies yielded T-cell immuno-dominant peptides. The protein-peptide interactions of the TLR-2 receptor showed good similarity scores in terms of the high number of hydrogen bonds compared to other protein-peptide interactions.
: The two epitopes predicted from
in the present investigation are promising vaccine candidates for targeting the TCS of
in systemic and nosocomial infections. This study also demonstrates an alternative strategy to tackling and mitigating MDR strains of
and provides a useful reference for the design and construction of novel vaccine candidates against this bacteria.
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