A Review of the Resistance Mechanisms for ß-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae.

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.

Unleashing the power of artificial intelligence for diagnosing and treating infectious diseases: A comprehensive review.

Infectious diseases present a global challenge, requiring accurate diagnosis, effective treatments, and preventive measures. Artificial intelligence (AI) has emerged as a promising tool for analysing complex molecular data and improving the diagnosis, treatment, and prevention of infectious diseases. Computer-aided detection (CAD) using convolutional neural networks (CNN) has gained prominence for diagnosing tuberculosis (TB) and other infectious diseases such as COVID-19, HIV, and viral pneumonia. The review discusses the challenges and limitations associated with AI in this field and explores various machine-learning models and AI-based approaches. Artificial neural networks (ANN), recurrent neural networks (RNN), support vector machines (SVM), multilayer neural networks (MLNN), CNN, long short-term memory (LSTM), and random forests (RF) are among the models discussed. The review emphasizes the potential of AI to enhance the accuracy and efficiency of diagnosis, treatment, and prevention of infectious diseases, highlighting the need for further research and development in this area.

Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis.

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.

Extended Spectrum- and Carbapenemase-Based ß-Lactam Resistance in the Arabian Peninsula-A Descriptive Review of Recent Years.

Antimicrobial resistance (AMR) is a global problem that also includes countries of the Arabian Peninsula. Of particular concern, is the continuing development of extended-spectrum ß-lactamases (ESBLs) in the countries of this region. Additionally, antibiotic treatment options for ESBL-producing bacteria are becoming limited, primarily due to the continuing development of carbapenem resistance (CR), carbapenems being frequently used to treat such infections. An overview of recent publications (2018-2021) indicates the presence of ESBL and/or CR in patients and hospitals in most countries of the Arabian Peninsula, although the delay between microbial isolation and publication inevitably makes an accurate analysis of the current situation rather difficult. However, there appears to be greater emphasis on CR (including combined ESBL and CR) in recent publications. Furthermore, although publications from Saudi Arabia are the most prevalent, this may simply reflect the increased interest in ESBL and CR within the country. Enhanced ESBL/CR surveillance is recommended for all countries in the Arabian Peninsula.

Regulation of Host Immune Response against Enterobacter cloacae Proteins via Computational mRNA Vaccine Design through Transcriptional Modification.

Enterobacter cloacae is mainly responsible for sepsis, urethritis, and respiratory tract infections. These bacteria may affect the transcription of the host and particularly their immune system by producing changes in their epigenetics. In the present study, four proteins of Enterobacter cloacae were used to predict the epitopes for the construction of an mRNA vaccine against Enterobacter cloacae infections. In order to generate cellular and humoral responses, various immunoinformatic-based approaches were used for developing the vaccine. The molecular docking analysis was performed for predicting the interaction among the chosen epitopes and corresponding MHC alleles. The vaccine was developed by combining epitopes (thirty-three total), which include the adjuvant Toll-like receptor-4 (TLR4). The constructed vaccine was analyzed and predicted to cover 99.2% of the global population. Additionally, in silico immunological modeling of the vaccination was also carried out. When it enters the cytoplasm of the human (host), the codon is optimized to generate the translated mRNA efficiently. Moreover, the peptide structures were analyzed and docked with TLR-3 and TLR-4. A dynamic simulation predicted the stability of the binding complex. The assumed construct was considered to be a potential candidate for a vaccine against Enterobacter cloacae infections. Hence, the proposed construct is suitable for in vitro analyses to validate its effectiveness.

Immune and Oxidative Response against Sonicated Antigen of Mycoplasma capricolum subspecies capripneumonia-A Causative Agent of Contagious Caprine Pleuropneumonia.

Vaccines are vital for prevention and control of mycoplasma diseases. The exploration of a vaccine candidate for the development of a vaccine is imperative. The present study envisages the evaluation of immune and oxidative response against an adjuvanted, sonicated antigen of Mycoplasma capricolum subsp. capripneumonia in male Angora rabbits (1 year old, 2 kg) divided in four groups, each having six animals. Group 1 was the healthy control and received 1 mL PBS via subcutaneous route. Group 2 was administered 1 mL of saponin-adjuvanted and -sonicated antigen, Group 3 was given 1 mL of montanide ISA 50-adjuvanted and-sonicated antigen, and Group 4 was given 1 mL of standard vaccine via subcutaneous route. Animals were evaluated for cellular and humoral immune response and oxidative parameters at 0, 7, 14, 21, and 28 days of the study. Total leukocytic, neutrophilic, and basophilic counts showed a significant (p < 0.05) increase in vaccinated groups compared to the healthy group on most of the intervals. TNF-α levels were significantly (p < 0.05) higher in the Group 2 than the Group 1 at all the time intervals and more comparable to Group 4 than Group 3. IL-10 levels were significantly (p < 0.05) higher in vaccinated groups compared to the healthy group on days 14, 21, and 28, but were lower in Group 3 than in Group 2 and Group 4. More hypersensitivity as inflammation and histopathological cellular infiltration in the ear was produced in Group 2 and Group 4 than in Group 3. IgG levels were significantly (p < 0.05) higher in Group 2 and Group 4 than in Group 3 on days 14 and 21. Antibody titers were comparatively higher in Group 4, followed by Group 2 and 3, than Group 1. Significantly (p < 0.05) higher oxidant and lower antioxidant values were noted in Group 2 and 4 compared to Group 3 and Group 1 on most of the intervals. The TLC and antibody titer showed increasing trend throughout the trial, whereas TNF-α, IgG, L, M and E started decreasing from day 14, and IL-10, N and B started decreasing from day 21. This study concludes that the saponin-adjuvanted and-sonicated antigen induces comparatively higher immune response than montanide but is associated with oxidative and inflammatory reactions.

Monkeypox and Its Possible Sexual Transmission: Where Are We Now with Its Evidence?

Monkeypox is a rare disease but is increasing in incidence in different countries since the first case was diagnosed in the UK by the United Kingdom (UK) Health Security Agency on 6 May 2022. As of 9 August, almost 32,000 cases have been identified in 89 countries. In endemic areas, the monkeypox virus (MPXV) is commonly transmitted through zoonosis, while in non-endemic regions, it is spread through human-to-human transmission. Symptoms can include flu-like symptoms, rash, or sores on the hands, feet, genitalia, or anus. In addition, people who did not take the smallpox vaccine were more likely to be infected than others. The exact pathogenesis and mechanisms are still unclear; however, most identified cases are reported in men who have sex with other men (MSM). According to the CDC, transmission can happen with any sexual or non-sexual contact with the infected person. However, a recent pooled meta-analysis reported that sexual contact is involved in more than 91% of cases. Moreover, it is the first time that semen analysis for many patients has shown positive monkeypox virus DNA. Therefore, in this review, we will describe transmission methods for MPXV while focusing mainly on potential sexual transmission and associated sexually transmitted infections. We will also highlight the preventive measures that can limit the spread of the diseases in this regard.

CTX-M-15 Positive Escherichia coli and Klebsiella pneumoniae Outbreak in the Neonatal Intensive Care Unit of a Maternity Hospital in Ha'il, Saudi Arabia.

OBJECTIVE: The aim of this study was to retrospectively characterize E. coli and K. pneumoniae isolates obtained from neonates during a suspected NICU outbreak of infection in Ha'il, Saudi Arabia during a period of one month (April 2014). METHODS: Antibiotic susceptibility patterns, molecular characterization for antibiotic-resistant genes (blaTEM, blaSHV, and blaCTX-M), and genotyping by PFGE and MLST were performed. RESULTS: A total of 24 E. coli and 48 K. pneumoniae isolates were cultured from neonates that had been admitted to the NICU. Among E. coli, the majority of isolates (19/24) were ESBL-positive and all of these nineteen (100%) harbored the CTX-M-15 gene. A total of 15% (3/19) were co-producers of CTX-M-15 and SHV-12, and 68.4% (13/19) were co-producers of CTX-M-15 and TEM-1. Among K. pneumoniae isolates, 87.5% (42/48) were ESBL positive with 92.85% (39/42) of these isolates containing the CTX-M-15 gene. A total of 97% (38/39) of K. pneumoniae were co-producers of CTX-M-15 and SHV-12, and 88% (37/42) were positive for TEM-1. Furthermore, 85.7% (36/42) K. pneumoniae were co-producers of CTX-M-15 and TEM-1. The majority of E. coli isolates (18/19 isolates) were grouped into two genetic clusters by pulsed field gel electrophoresis (PFGE) and all the isolates were found to be ST-131 type. In contrast, K. pneumoniae (31/42) isolates belonged to a single genotypic lineage, and all (100%) isolates belonged to the ST-14 type. CONCLUSION: This is the first report of CTX-M-15-positive, ESBL E. coli, and K. pneumoniae isolates recovered from an outbreak in an NICU in Ha'il, Saudi Arabia. It is alarming to note the high rate of outbreak isolates with simultaneous production of CTX-M-15 and SHV-12 conferring high-level resistance to oxyimino-cephalosporins.

Rapid identification of Nocardia cyriacigeorgica from a brain abscess patient using MALDI-TOF-MS.

Nocardia cyriacigeorgica (N. cyriacigeorgica) is most frequently associated with human infections, including chronic bronchitis, pulmonary disease and brain abscesses. In general, N. cyriacigeorgica causes infections in immunocompromised individuals and has been reported in clinical samples worldwide. However, the isolation and speciation of N. cyriacigeorgica in the routine diagnostic microbiology laboratory are complicated and time consuming. Recent mass spectrometry techniques such as matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) have been successfully integrated into many routine diagnostic microbiology laboratories, allowing for the rapid, accurate and simple identification and speciation of many different microorganisms, including difficult-to-identify bacterial species. Here, we present a case report of a 65-year-old female patient from the neurology ward of Prince Sultan Military Medical City in Riyadh, Saudi Arabia, who was infected with N. cyriacigeorgica. The bacterium was successfully identified by MALDI-TOF-MS, with species identification subsequently confirmed by sequence analysis of the 16S ribosomal RNA.

Survival and reduction in foodborne bacteria using methyl cellulose film doped with europium oxide nanoparticles.

The study validated the efficacy of methyl cellulose films doped with different concentration of Eu2O3 nanoparticles to inactivate foodborne pathogens. Eu2O3 nanoparticles were added to the methyl cellulose solution with different weight percentages (0.0, 0.5, 0.75, 1.0, 1.25, and 1.5 wt%). X-ray diffraction patterns for the prepared films were studied. A significant lower count of E. coli, S. typhimurium, and S. aureus (p ≤ .05) inoculated in MC films doped with Eu2O3 nanoparticles compared with pure MC film could be achieved. The findings acquired verify the impact of prepared MC films doped with Eu2O3 nanoparticles on the test strains.

Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for identification of Clostridium species isolated from Saudi Arabia

Abstract The aim of this study was to identify different Clostridium spp. isolated from currency notes from the Ha’il region of Saudi Arabia in September 2014 using MALDI–TOF-MS. Clostridium spp. were identified by Bruker MALDI–TOF-MS and compared with VITEK 2. The confirmation of the presence of different Clostridium spp. was performed by determining the sequence of the 16S ribosomal RNA gene. In this study, 144 Clostridium spp. were isolated. Among these specimens, MALDI–TOF-MS could identify 88.8% (128/144) of the isolates to the species level and 92.3% (133/144) to the genus level, whereas, VITEK 2 identified 77.7% of the (112/144) isolates. The correct identification of the 144 isolates was performed by sequence analysis of the 500 bp 16S rRNA gene. The most common Clostridium spp. identified were Clostridium perfringens (67.36%), Clostridium subterminale (14.58%), Clostridium sordellii (9%) and Clostridium sporogenes (9%). The results of this study demonstrate that MALDI–TOF-MS is a rapid, accurate and user friendly technique for the identification of Clostridium spp. Additionally, MALDI–TOF-MS has advantages over VITEK 2 in the identification of fastidious micro-organisms, such as Clostridium spp. Incorporating this technique into routine microbiology would lead to more successful and rapid identification of pathogenic and difficult to identify micro-organisms.

Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for identification of Clostridium species isolated from Saudi Arabia.

The aim of this study was to identify different Clostridium spp. isolated from currency notes from the Ha'il region of Saudi Arabia in September 2014 using MALDI-TOF-MS. Clostridium spp. were identified by Bruker MALDI-TOF-MS and compared with VITEK 2. The confirmation of the presence of different Clostridium spp. was performed by determining the sequence of the 16S ribosomal RNA gene. In this study, 144 Clostridium spp. were isolated. Among these specimens, MALDI-TOF-MS could identify 88.8% (128/144) of the isolates to the species level and 92.3% (133/144) to the genus level, whereas, VITEK 2 identified 77.7% of the (112/144) isolates. The correct identification of the 144 isolates was performed by sequence analysis of the 500bp 16S rRNA gene. The most common Clostridium spp. identified were Clostridium perfringens (67.36%), Clostridium subterminale (14.58%), Clostridium sordellii (9%) and Clostridium sporogenes (9%). The results of this study demonstrate that MALDI-TOF-MS is a rapid, accurate and user friendly technique for the identification of Clostridium spp. Additionally, MALDI-TOF-MS has advantages over VITEK 2 in the identification of fastidious micro-organisms, such as Clostridium spp. Incorporating this technique into routine microbiology would lead to more successful and rapid identification of pathogenic and difficult to identify micro-organisms.