Effect of C7-3-Peptide-Loaded Chitosan Nanoparticles Against Multi-Drug-Resistant Neisseria gonorrhoeae.

Introduction: The emergence of Neisseria gonorrhoeae-resistant strains represents one of the most urgent global threats. In this regard, C7-3 peptide is one of the anti-virulence therapies that has demonstrated promising anti-gonococcal activity. Accordingly, this research aimed to formulate C7-3 peptide and its derivatives in chitosan nanoparticles. Methods: The peptide loaded chitosan nanoparticles were prepared using ion gelation method, and their physicochemical characteristics were investigated. The anti-gonococcal and antibiofilm activity of prepared NPs was assessed, and their cytotoxicity in human ovarian cells was evaluated. Results: All prepared NPs were optimized for the smallest particle size of 136.9 to 168.3 nm. The EE% of C7-3, C7-3m1, and C7-3m2 CNPs reached 90.2, 92.5, and 91.8%, respectively. An in vitro release study demonstrated a continuous sustained-release pattern of C7-3 peptide from NPs. The SDS-PAGE assay confirmed the integrity of C7-3 peptide after the fabrication process. When comparing each peptide alone, the generated NPs demonstrated higher anti-gonococcal and anti-biofilm effectiveness against standard and resistant bacterial strains under anaerobic conditions. The cytotoxicity experiments revealed the cytocompatibility of NPs in HeLa cell lines. Given the advantages of enhanced anti-gonococcal activity of the C7-3 peptide and its derivatives when loaded with CNPs, as well as the antimicrobial properties of chitosan NPs, the reported NPs have great potential in the treatment of gonococcal infection.

Knowledge and behaviors of using vitamin D to boost immunity against COVID-19 pandemic: A cross-sectional study in Saudi Arabia.

The coronavirus 2019 (COVID-19) pandemic has globally impacted all aspects of life since its emergence and spread. There is a strong biological assumption and progressing epidemiological data supporting the role of vitamin D (VD) in COVID-19 infection. This study aims to determine the knowledge about VD supplements to boost immunity against COVID-19 and if participation in specific behaviors has increased the consumption of VD supplements during social distance restriction in Saudi Arabia (SA) in May 2021. This cross-sectional study used a structured online questionnaire for 2369 SA people, including demographic characteristics and knowledge about VD supplements to boost immunity against COVID-19 showed that there was a significant association between sex and vitamin D deficiency (VDD) (P = .000), and having VDD was strongly associated with having another vitamin deficiency (P = .008). Additionally, there was a statistically significant difference between VDD and cardiovascular (P = .027) and respiratory diseases (P = .019). Almost half of the participants used VD supplements to reduce or heal their COVID-19 symptoms. The adverse association between having VDD and understanding of COVID-19 symptoms was statistically significant (P = .01). Ginger is commonly used as an alternative medicine for the treatment of VD. The administration of VD is now known to be of physiological significance for general health, and evidence suggesting the beneficial role of VD in the prevention and/or treatment of diseases, particularly infectious diseases, such as COVID-19, is increasing.

Evaluation of the Clinical Outcome and Cost Analysis of Antibiotics in the Treatment of Acute Respiratory Tract Infections in the Emergency Department in Saudi Arabia.

This study aims to assess the prevalence and antibiotic-treatment patterns of respiratory tract infections (RTIs), prevalence and types of antibiotic-prescribing errors, and the cost of inappropriate antibiotic use among emergency department (ED) patients. A cross-sectional study was conducted at the ED in King Abdulaziz Medical City, Riyadh, Saudi Arabia. Patient characteristics (age, sex, weight, allergies, diagnostic tests (CX-Ray), cultures, microorganism types, and prescription characteristics) were studied. During the study, 3185 cases were diagnosed with RTIs: adults (>15 years) 55% and pediatrics (<15 years) 44%. The overall prevalence of RTIs was 21%, differentiated by upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) (URTI 13.4%; LRTI 8.4%), of total visits. Three main antibiotics (ATB) categories were prescribed in both age groups: penicillin (pediatrics 43%; adults 26%), cephalosporin (pediatrics 29%; adults 19%), and macrolide (pediatrics 26%; adults 38%). The prevalence of inappropriate ATB prescriptions was 53% (pediatrics 35%; adults 67%). Errors in ATB included selection (3.3%), dosage (22%), frequency (3%), and duration (32%). There is a compelling need to create antimicrobial stewardship (AMS) programs to improve antibiotic use due to the high number of prescriptions in the ED deemed as inappropriate. This will help to prevent unwanted consequences on the patients and the community associated with antibiotic use.

Attenuation of Pseudomonas aeruginosa Quorum Sensing Virulence of Biofilm and Pyocyanin by mBTL-Loaded Calcium Alginate Nanoparticles.

Pseudomonas aeruginosa contributes to many chronic infections and has been found to be resistant to multiple antibiotics. Pseudomonas use a quorum sensing system (QS) to control biofilm establishment and virulence factors, and, thus, quorum sensing inhibitors (QSIs), such as meta-bromo-thiolactone (mBTL), are promising anti-infective agents. Accordingly, this study intended to investigate the antibacterial and anti-virulence activity of mBTL-loaded calcium alginate nanoparticles (CANPs) against Pseudomonas aeruginosa and different QS mutants. The results show that the mBTL-CANPs had higher antibacterial activity, which was made evident by decreases in all tested strains except the ∆lasR/∆rhlR double mutant, with MIC50 (0.5 mg/mL) of mBTL-CANPs compared with free mBTL at MIC50 (˃1 mg/mL). The biofilm formation of P. aeruginosa and some QS-deficient mutants were reduced in response to 0.5-0.125 mg/mL of mBTL-encapsulating CANPs. The pyocyanin production of the tested strains except ∆lasA and ∆rhlR decreased when challenged with 0.5 mg/mL of mBTL-loaded NPs. The subsequent characterization of the cytotoxic effect of these NPs on human lung epithelial cells (A549) and cystic fibrosis fibroblast cells (LL 29) demonstrated that synthesized NPs were cytocompatible at MIC50 in both cell lines and markedly reduced the cytotoxic effect observed with mBTL alone on these cells. The resulting formulation reduced the P. aeruginosa strains' adhesion to A549 comparably with mBTL, suggesting their potential anti-adhesive effect. Given the virulence suppressing action, cytocompatibility, and enhanced anti-biofilm effect of mBTL-CANPs, and the advantage of alginate-based NPs as an antimicrobial delivery system these nanoparticles have great potential in the prophylaxis and treatment of infection caused by Pseudomonas aeruginosa.

Preparation and characterization of Meta-bromo-thiolactone calcium alginate nanoparticles.

Recently, the focus has been shifting toward Quorum sensing inhibitors which reduce Pseudomonas aeruginosa virulence factors, alleviating infections. In this work, me-ta-bromo-thiolactone (mBTL), a potent quorum and virulence inhibitor for the Pseudomonas aeruginosa strains, were formulated in calcium alginate nanoparticles (CANPs). Alginate is used as nutrients and as backbone virulence aspect for Pseudomonas and therefore was chosen. mBTL-loaded-CANPs were characterized for particle size, polydispersity index, zeta potential, morphology visualized by Transmission Electron Microscopy (TEM) and drug release profile. Chemical and physical analysis of formulated mBTL-loaded-CANPs were evaluated using Fourier transform infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC) and Physical stability of mBTL-loaded-CANPs assessed at various temperature 25 ± 1 °C, 4 ± 0.5 °C and -30° ± 1 °C over a period of 4 and 9 months. Synthesized CANPs showed nano-size particles ranging from 140 to 200 nm with spherical particles for plain CANPS and irregular shape for mBTL-loaded-CANPs with a sustainable release profile over 48hrs. FTIR showed stable structure of loaded-mBTL and DSC displayed no interaction between mBTL and polymer. State of released mBTL from CANPs kept at 25 °C, 4 °C and -30 °C over 4 and 9 months showed stable formula at room temperature which kept as a goal of nanoparticles storage. The findings of this study revealed successful preparation of mBTL-loaded-CANPs.

Risk management and infection control preparedness of Saudi healthcare facilities to overcome the COVID-19 pandemic.

Objective: To evaluate the preparedness of Saudi healthcare facilities to handle the coronavirus disease 2019 (COVID-19) pandemic. Methods: Between April and June 2020, a cross-sectional study was conducted among Saudi hospitals using an online-administered English-language questionnaire by the Saudi Commission for Health Specialties. The questionnaire evaluates all aspects of risk management, infection control and preventative programmes that should be known and practised by all healthcare workers (HCWs). All HCWs in Saudi hospitals designated to accept patients with COVID-19 were involved in the study. Results: In total, 161 HCWs responded to the survey. General understanding of hospital risk management plans and infection prevention measures was found to be outstanding (80.4%), with no differences in responses by gender, education or occupation. Some differences in responses were found by age group and years of working experience. Most responses were from hospitals located in the Central Province (72.7%) and governmental hospitals (88%), and most provided family services (68%). Furthermore, the results showed that medical professionals received adequate training, which is recognized as the baseline for effective risk management and infection control and prevention procedures, policies and recommendations. Conclusions: Notwithstanding small differences between HCWs, this study found that all HCWs in Saudi hospitals had excellent knowledge of risk management plans and pandemic sub-plans of infection control and prevention policies, procedures and principles, which has aided the health authorities in Saudi Arabia in mitigating COVID-19 effectively.

MicroRNA-219 loaded chitosan nanoparticles for treatment of glioblastoma.

Recent evidence has implicated microRNA-219 (miR-219) in regulation of gene contributed in glioblastoma (GBM) pathogenesis. This study aimed to prepare miR-219 in chitosan (CS) nanoparticles (NPs), characterize and investigate their efficacy on human GBM cell line (U87 MG). NPs were prepared using ionic gelation method. The influence of process parameters on physicochemical characteristics of NPs was investigated. Apoptotic effect of miR-219 was examined on U87 MG cells. Formulated NPs showed particle size of 109 ± 2.18 nm, with poly dispersity index equal to 0.2 ± 0.05, and zeta potential of +20.5 ± 0.7 mV. Entrapment efficiency of miR-219 in loaded NP has reached 95%. The in vitro release study demonstrated sustained release pattern of miR-219 from CS-NPs. Gel retardation assay has confirmed the integrity of miR-219 after production process. The fabricated NPs reduced the survival of U87 MG cells to 78% after 24 h of post-transfection, and into 67.5% after 48 h. However, fibroblasts were not affected by the NPs, revealing their specificity for GBM cells. Given the tumour suppressing function of miR-219, and advantage of CS-NPs for gene delivery to the central nervous system, the presented NPs have a great potential for treatment of GBM.

Association Between Obesity and COVID-19 Disease Severity in Saudi Population.

Background: The persistent coronavirus disease 2019 (COVID-19) outbreak has placed a significant burden on the scientific and medical professions. The study examined the association between body mass index (BMI), stratified by category, and severe form of COVID-19, and to explore the influence of demographic characteristics and other known risk factors. Methods: This was a retrospective analysis based on COVID-19 data from the Saudi Arabian Ministry of Health. Data were collected for all patients admitted to three main hospitals in Riyadh region between March 1st and July 30, 2020. The effects of BMI, demographic characteristics, clinical presentation, and comorbidities on infection severity were investigated. Results: A total of 950 patients were included in the study (70% male, 85% aged younger than 60 years old). A total of 55 (5.8%) patients were underweight, 263 (27.7%) were normal weight, 351 (37%) were overweight, 161 (17%) were obese class I, 76 (8%) were obese class II, and 44 (4.6%) were obese class III. Cough, fever, and shortness of breath were the most common symptoms among overweight patients. According to the findings of a bivariate logistic regression study, class III obesity was significantly associated with a more severe form of COVID-19 (odds ratio, 2.874; 95% confidence interval, 1.344-6.149). Conclusion: This study revealed that patients with a BMI ≥40 kg/m2 had a higher risk of severe COVID-19 than those with normal weight. This suggests that obesity is a risk factor for severe COVID-19 and influences disease presentation.

MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization.

Choroidal neovascularization (CNV) is a major cause of visual impairment that results from excessive growth of blood vessels in the eye's choroid. The limited clinical efficacy of the current therapy for this condition requires the emergence of new treatment modalities such as microRNA (miRNAs). A recent study identified microRNA-539-5p (miR-539) as an angiogenic suppressor in a CNV animal model; however, its therapeutic delivery is limited. Therefore, this study aims to formulate miR-539 in targeted nanoparticles (NPs) prepared from polylactic-co-glycolic acid (PLGA). The NPs were decorated with internalizing arginylglycylaspartic (RGD) peptide (iRGD), which specifically targets the alpha-v-beta-3 (αvß3) integrin receptor that is overexpressed in blood vessels of ocular tissue in CNV patients. The 1H NMR spectra results revealed successful conjugation of iRGD peptide into PLGA NPs. The miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs were prepared and showed a particle size of 300 ± 3 and 306.40 ± 4 nm, respectively. A reduction in human retinal microvascular endothelial cell (HRMEC) viability was shown 48 and 72 h post transfection with miR-539 incorporated in PLGA NPs and iRGD-PLGA.NPs. iRGD-functionalized PLGA NPs caused further significant reduction in cell viability when compared with plain ones, revealing an enhancement in the NP uptake with iRGD-grafted NPs. The current study showed that miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs are promising approaches that reduced the viability of HRMECs, suggesting their therapeutic potential in the treatment of CNV.

Molecular Pathogenesis of Colorectal Cancer with an Emphasis on Recent Advances in Biomarkers, as Well as Nanotechnology-Based Diagnostic and Therapeutic Approaches.

Colorectal cancer (CRC) is a serious disease that affects millions of people throughout the world, despite considerable advances in therapy. The formation of colorectal adenomas and invasive adenocarcinomas is the consequence of a succession of genetic and epigenetic changes in the normal colonic epithelium. Genetic and epigenetic processes associated with the onset, development, and metastasis of sporadic CRC have been studied in depth, resulting in identifying biomarkers that might be used to predict behaviour and prognosis beyond staging and influence therapeutic options. A novel biomarker, or a group of biomarkers, must be discovered in order to build an accurate and clinically useful test that may be used as an alternative to conventional methods for the early detection of CRC and to identify prospective new therapeutic intervention targets. To minimise the mortality burden of colorectal cancer, new screening methods with higher accuracy and nano-based diagnostic precision are needed. Cytotoxic medication has negative side effects and is restricted by medication resistance. One of the most promising cancer treatment techniques is the use of nano-based carrier system as a medication delivery mechanism. To deliver cytotoxic medicines, targeted nanoparticles might take advantage of differently expressed molecules on the surface of cancer cells. The use of different compounds as ligands on the surface of nanoparticles to interact with cancer cells, enabling the efficient delivery of antitumor medicines. Formulations based on nanoparticles might aid in early cancer diagnosis and help to overcome the limitations of traditional treatments, including low water solubility, nonspecific biodistribution, and restricted bioavailability. This article addresses about the molecular pathogenesis of CRC and highlights about biomarkers. It also provides conceptual knowledge of nanotechnology-based diagnostic techniques and therapeutic approaches for malignant colorectal cancer.

Preventing SARS-CoV-2 transmission in the emergency department by implementing a separate pathway for patients with respiratory conditions.

OBJECTIVES: This study aimed to describe the development and implementation of a separated pathway to check and treat patients with a suspected/confirmed coronavirus disease 2019 (COVID-19) in the emergency department (ED) at King Abdullah bin Abdulaziz University Hospital in Riyadh. METHODS: We conducted a retrospective, descriptive longitudinal study from March to July 2020 by analyzing data of all confirmed cases of COVID-19 among ED visitors and healthcare workers in King Abdullah bin Abdulaziz University Hospital. RESULTS: During the study period, a total of 1,182 swab samples were collected for testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 285 (24.1%) tested positive. Of the 285 cases of confirmed SARS-CoV-2 infection, 18 were healthcare workers and 267 were patients. As a result of using the respiratory pathway for COVID-19 patients, the hospital managed to limit transmission of SARS-CoV-2 not only between patients but also between patients and healthcare workers, while also containing the pandemic. There were no cases of nosocomial SARS-CoV-2 infection recorded among the patients who visited the ED or the flu clinic. All confirmed cases were community acquired and patients were cared for under constrained measures. CONCLUSIONS: Implementing infection control measures and restricting those with respiratory symptoms to the ED pathway prevented nosocomial spread of SARS-CoV-2 infection in the ED.

Outcomes associated with tocilizumab with or without corticosteroid versus dexamethasone for treatment of patients with severe to critical COVID-19 pneumonia.

INTRODUCTION: Immunomodulators, including dexamethasone (DEX), have been recommended by the Infectious Disease Society of America (IDSA) to treat moderate, severe, and critical COVID-19. Tocilizumab (TCZ) was added to the treatment recommendations based on recent data from two large randomized controlled trials and its potential synergistic effect with DEX. METHOD: We included adult patients admitted from June until October 2020 with a PCR confirmed SARS-CoV-2 infection. 135 patients with severe to critical COVID-19 and received TCZ and/or corticosteroid or DEX were retrospectively evaluated and followed until hospital discharge or death. RESULTS: The cohort was divided into two different groups of patients; TCZ group received TCZ ± corticosteroid, N = 100 and DEX group received DEX, N = 35. Groups were analyzed for hospital mortality. The rate of hospital mortality was 36% in TCZ and 37% in the DEX group, p = 0.91. Age of 60 years and above was associated with higher mortality rate with OR = 1.030 and 95% CI = (1.004, 1.057). More than 50% of patients required MV in both groups. Development of bacterial or fungal infection post immunomodulator were similar in TCZ and DEX groups, 29% vs. 31.4%. CONCLUSION: Our study revealed that age of 60 years and above is the only factor associated with higher mortality rate regardless of the type of immunomodulator therapy. Findings of this study also revealed the lack of synergistic effect between TCZ and DEX on the hospital mortality.

Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationship of Substituted Quinazolinones as Cyclin-Dependent Kinase 9 Inhibitors.

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 µM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski's rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.

Bacteria from Infectious Particles to Cell Based Anticancer Targeted Drug Delivery Systems.

Bacterial ghosts (BGs) are empty cell envelopes of nonliving evacuated bacterial cells. They are free from their cytoplasmic contents; however, they sustain their cellular 3D morphology and antigenic structures, counting on bioadhesive properties. Lately, they have been tested as an advanced drug delivery system (DDS) for different materials like DNA, peptides, or drugs, either single components or combinations. Different studies have revealed that, BG DDS were paid the greatest attention in recent years. The current review explores the impact of BGs on the field of drug delivery and drug targeting. BGs have a varied area of applications, including vaccine and tumor therapy. Moreover, the use of BGs, their synthesis, their uniqueness as a delivery system and application principles in cancer are discussed. Furthermore, the safety issues of BGs and stability aspects of using ghost bacteria as delivery systems are discussed. Future perspective efforts that must be followed for this important system to continue to grow are important and promising.

Improved delivery of miR-1296 loaded cationic nanoliposomes for effective suppression of triple negative breast cancer.

Nowadays, microRNA is considered an attractive strategy for the effective treatment of cancer. A significant delivery of microRNA for cancer therapy remains a significant obstacle to target cancer cells. The restoring microRNA-1296 (miR-1296) has immense therapeutic efficacy in triple-negative breast cancer (TNBC). TNBC is an aggressive subtype of breast tumors with the progression of malignant transformation. This study aimed to develop a cationic nanoliposome that can serve as a miR-1296 carrier and studied its efficiency in TNBC. The efficacy of miR-1296 liposomes was evaluated on its apoptotic effect, cellular uptake, and potential chemotherapy sensitization in the TNBC cell line (MDA-MB-231). For in vitro viability study, the apoptotic effect was performed to validate protein expression using Alamar blue kit and western blot. The transfection of miR-1296 into TNBC cells was also investigated using cisplatin as a TNBC resistance drug. The fluorescent miR-1296-cy3 liposome was used for cellular uptake study. The miR-liposome was successfully prepared with a particle size of 123.6 ± 1.3 nm and encapsulation efficiency of 94.33%. A dose of 0.5 uM has significantly reduced the viability of MDA-MB-231 to be 33.45%±5.29 (P < 0.001). This result was validated by down-expression of CCND1, and PARP1, the miR-1296 receptor, and apoptosis marker. The image of the miR-1296-cy3 liposome showed cytoplasmic intracellular localization. It was found high sensitization of TNBC cell line for miR-1296 liposome compared to cisplatin (P < 0.001). Future in vivo research may answer questions concerning safety and stability. This study demonstrates that miR-191 liposomes may have promising clinical applications for TNBC therapy.

Awareness and knowledge of COVID-19 infection control precautions and waste management among healthcare workers: Saudi cross-sectional study.

ABSTRACT: Healthcare workers (HWs) perform a critical role not only in the clinical management of patients but also in providing adequate infection control and prevention measures and waste management procedures to be implemented in healthcare facilities. The aim of this study was to evaluate the awareness and knowledge of COVID-19 infection control precautions and waste management procedures among HWs in Saudi Arabian hospitals.This was a descriptive, cross-sectional study. Information on knowledge, awareness, and practice of infection control and waste management procedures were obtained from the HWs using a structured questionnaire. A thematic analysis was used to analyze the data.Our findings indicated that most of the study participants were knowledgeable, with a mean score of 78.3%. In total, 92.5%, 90.3%, and 91.7% of the participants were aware of the infection control precautions, COVID-19 waste management procedures, the availability of infection control supplies, respectively. HWs' Knowledge regarding waste management and infection control procedures correlated significantly with sex (P ≤ .001 and <.001), education (P = .024 and .043), and working experience (P = .029 and .009), respectively.Most participants appreciated the importance of their role in infection control, surveillance, and monitoring of the ongoing safety practices in their patients as well as their facilities and communities.

Impact of Rapid Identification of Staphylococcus Species in Positive Blood Culture Using GeneXpert Methicillin-Resistant Staphylococcus aureus/ Staphylococcus aureus Blood Culture Assay Combined with Antibiotic Stewardship.

Staphylococcus aureus bacteremia is a life-threatening condition associated with a substantial financial burden on the health care system. The use of the GeneXpert® methicillin-resistant S. aureus (MRSA)/S. aureus blood culture (BC) test for the identification of S. aureus may influence antibiotic stewardship and clinical outcomes. This study assessed the clinical and financial impact of utilizing GeneXpert MRSA/SA in combination with criterion-based testing. The outcomes between October 1, 2018, and June 30, 2019, were evaluated in 65 adult patients who had positive BCs with Gram-positive cocci in clusters. GeneXpert MRSA/SA significantly shortened the time to optimal antimicrobial therapy by 1.7 days (2.5 vs. 44 hr, p < 0.0001). The cost saved because of interventions based on GeneXpert testing results was $4,121. GeneXpert testing has shortened the time to optimal therapy and positively impacted cost, although it had no significant effect on length of hospital stay and mortality rate.

Evaluating the effect of antibiotics sub-inhibitory dose on Pseudomonas aeruginosa quorum sensing dependent virulence and its phenotypes.

The opportunistic Pseudomonas aeruginosa virulence controlled by quorum sensing (QS) also identified as, cell-cell communication. QS system is organized by the LasI-LasR and the RhlI-RhlR components. Provided that QS tends to perform a key role in virulence gene expression and host defence function, QS inhibitors have been proposed as potential antipseudomonal therapies. Sub-inhibitory concentrations (sub-MIC) of antibiotics, although having biostatic effect on bacteria, but can interfere with bacterial QS system and virulence. This research aimed to examine the impact of sub-MIC of azithromycin, imipenem, cefepime and piperacillin/tazobactam on the QS-dependent virulence including pyocyanin and biofilm production, haemolysin, protease and DNase in P. aeruginosa wildtype and mutant strains; transcriptional-regulator (ΔLasR), autoinducer synthesis protein (ΔLasI), transcriptional-regulator (ΔRhlR), protease precursor (ΔLasA) and double regulators mutants (ΔLasR/RhlR). The growth of all strains showed similar pattern, however, in presence of antibiotics significant growth variation was observed among mutant strains when compared to wild type strain. Antimicrobial activity tested by agar diffusion method of all antibiotics on all strains were used to compare the zones of therapeutic and sub-MIC doses showing a significant difference in the inhibition zone. QS-dependant virulence as biofilm, pyocyanin, protease, haemolysin and DNase production showed significant variation on all strains compared to wild type in response to antibiotics used at sub-MIC doses. In conclusion well known antibiotics can be used in sub-MIC doses to decrease the virulence of P. aeruginosa in addition to overcoming the major side effect of the high doses and the occurrence of resistance.

Formulation and in vitro and in vivo evaluation of surfactant-stabilized mucoadhesive nanogels for vaginal delivery of fluconazole.

Surfactant-stabilized mucoadhesive nanogels (NGs) for vaginal delivery of fluconazole (FLZ) were studied and evaluated in this work. FLZ-NG formulations were prepared using two different types of mucoadhesive polymers, Carbopol 934 (Ca934) and Pluronic F-127 (PF127). A rheology study revealed a non-Newtonian pseudoplastic flow behavior (shear thinning) in the prepared NGs. The viscosity of Ca934 NG (0.47 Pa s) was much lower compared to the PF127 NG (6.10 Pa s). The rheology study results correlated well with the in vitro FLZ release profile from the NG formulations. A pH study (pH = 3.90-4.90) revealed that the formulations were physiologically suitable for vaginal application, to avoid the irritation of the vaginal mucosa. Finally, in vitro and in vivo antimicrobial tests were performed. FLZ incorporated into the Ca934 gel had the strongest antimicrobial effect, with a mean inhibition zone of 24 ± 1.6 mm. Based on these results, it was concluded that the mucoadhesive NG incorporating FLZ resulted in a sustained release and enhanced antimicrobial effect, which would enhance and prolong the therapeutic effects of vaginally delivered FLZ.

Influence of the minimum inhibitory concentration of daptomycin on the outcomes of Staphylococcus aureus bacteraemia.

OBJECTIVES: Recent studies have shown that methicillin-resistantStaphylococcus aureus (MRSA) bacteraemia with vancomycin minimum inhibitory concentration (MIC) >1 µg/mL is associated with a higher rate of treatment failure and a higher mortality rate. Daptomycin is an alternative to vancomycin but has not been as well studied. The aim of this literature review was to evaluate the effect of daptomycin MIC on the outcomes of S. aureus bacteraemia. METHODS: We conducted a literature search for the period January 2010 to January 2019 using the MEDLINE and Embase databases. RESULTS: Four studies were included in the review. The outcomes were clinical cure and 30- or 60-day mortality. In two retrospective studies, 60-70% ofS. aureus isolates had a low daptomycin MIC (≤0.5 µg/mL) and patients with MRSA bacteraemia who were treated with daptomycin had a lower mortality rate. In another study, patients with methicillin-susceptible S. aureus bacteraemia with low daptomycin MICs had a lower risk of developing septic thrombophlebitis. One study showed that patients with MRSA bacteraemia had a higher mortality rate if the daptomycin MIC was >0.5 µg/mL. CONCLUSION: The included studies in this review suggest a possible association between high daptomycin MIC and unfavourable clinical outcomes ofS. aureus bacteraemia. Further prospective studies are required to evaluate the impact of the daptomycin MIC on the clinical outcomes of S. aureus bacteraemia.