Partnering essential oils with antibiotics: proven therapies against bovine Staphylococcus aureus mastitis.

Introduction: There is an urgent need to develop therapeutic options for biofilm-producing Staphylococcus aureus (S. aureus). Therefore, the renewed interest in essential oils (EOs), especially carvacrol, linalool and eugenol, has attracted the attention of our research group. Methods: Multidrug resistance and multivirulence profiles in addition to biofilm production of S. aureus strains isolated from cows with mastitis were evaluated using both phenotypic and genotypic methods. The antimicrobial and antibiofilm activities of EOs were tested using both in vitro and molecular docking studies. Moreover, the interactions between commonly used antibiotics and the tested EOs were detected using the checkerboard method. Results: We found that all our isolates (n= 37) were biofilm methicillin resistant S. aureus (MRSA) producers and 40.5% were vancomycin resistant S. aureus (VRSA). Unfortunately, 73 and 43.2% of the recovered MRSA isolates showed multidrug resistant (MDR) and multivirulence patterns, respectively. The antimicrobial activities of the tested EOs matched with the phenotypic evaluation of the antibiofilm activities and molecular docking studies. Linalool showed the highest antimicrobial and antibiofilm activities, followed by carvacrol and eugenol EOs. Fortunately, synergistic interactions between the investigated EOs and methicillin or vancomycin were detected with fractional inhibitory concentration index (FICI) values ≤ 0.5. Moreover, the antimicrobial resistance patterns of 13 isolates changed to sensitive phenotypes after treatment with any of the investigated EOs. Treatment failure of bovine mastitis with resistant S. aureus can be avoided by combining the investigated EOs with available antimicrobial drugs. Conclusion: We hope that our findings can be translated into a formulation of new pharmaceutical dosage forms against biofilm-producing S. aureus pathogens.

What Is behind the Correlation Analysis of Diarrheagenic E. coli Pathotypes?

The treatment failure recorded among patients and animals infected with diarrheagenic Escherichia coli (DEC) was increased due to the presence of specific virulence markers among these strains. These markers were used to classify DEC into several pathotypes. We analyzed the correlations between DEC pathotypes and antimicrobial resistances, the existence of virulence genes, serotypes, and hosts. The ETEC pathotype was detected with a high prevalence rate (25%). Moreover, the ETEC and EPEC pathotypes were highly associated with human infections in contrast to the EIEC and EAEC phenotypes, which were commonly recognized among animal isolates. Interestingly, the antimicrobial resistance was affected by E. coli pathotypes. With the exception of EIEC and STEC, imipenem represented the most effective antibiotic against the other pathotypes. There were fixed correlations between the DEC pathotypes and the presence of virulence markers and hosts; meanwhile, their correlation with serotypes was variable. Additionally, the vast majority of our isolates were highly diverse, based on both phenotypic and ERIC molecular typing techniques. Our promising results gave a clear indication for the heterogeneity and weak clonality of DEC pathotypes in Egypt, which can be utilized in the evaluation of the current therapeutic protocols and infection control guidelines.

Hospital Pharmacists Interventions to Drug-Related Problems at Tertiary Critical Care Pediatric Settings in Jazan, Saudi Arabia.

Background: While drug-related problems (DRPs) have been recognized as a major concern in pediatric wards, the role of hospital pharmacy in improving medication safety has been rarely studied. Objectives: To investigate the frequency, nature, and severity of DRPs and associated pharmacist interventions (PIs). Methods: This is a prospective study carried out using direct observation over a year (2019-2020) in 3 pediatric wards (pediatric emergency department (PED), pediatric intensive care unit (PICU), and neonatal intensive care unit (NICU) in Jazan, Saudi Arabia. A validated data reporting form was developed to include comprehensive clinical data about the prescribed medications, characteristics of patients, and PIs upon DRPs. Clinical significance of DRPs was evaluated by an expert panel, which comprised a clinical pharmacist, a pediatrician, and an internist. Data analysis was conducted using SPSS V26. Results: The overall incidence of DRPs was 6.6%. The highest rate of DRPs 15.2% was detected in the pediatric ICU. Of the 596 DRPs detected, 10.2% were inappropriate drug choice, 5.2% were rated major DRPs, and one-third 33.2% were related to the digestive system and metabolism. Dosing problems were the most predominant DRPs across the included wards. A higher proportion of clinically major and moderate DRPs were detected in pediatric ED. Telephone-delivered interventions [OR: 1.72: 95%CI: 0.78-2.57: P = .001], too high dose [OR: 2.64: 95%CI: 1.33-4.56: P = .01], and major DRPs [OR: 3.21: 95%CI: 2.15-6.42: P = .04] were significant predictors for acceptance of PIs. Conclusion: DRPs are common in Saudi pediatric wards and many of these incidents were clinically major and moderate. Telephone-delivered interventions, too high dose, and major DRPs were major predictors for physician acceptance of PIs.

Clonal Diversity and Epidemiological Characteristics of ST239-MRSA Strains.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen associated with severe morbidity and mortality and poses a significant threat to public health worldwide. The genetic diversity based on sequence types of MRSA strains was illustrated in previous studies; meanwhile, the diversity along with the predominant sequence type, especially in Egypt, remains unknown. The purpose of the current study was to determine the diversity of the predominant MRSA clone ST239-MRSA (n = 50) isolated from different hosts and clinical samples and to illustrate the correlation between the resistance patterns, toxin genes, and the genetic background in Port-said and El-Sharkia Governorates, Egypt. The ST239-MRSA clone was analyzed by phenotypic antibiotyping and various genotypic assays comprising SCCmec, agr, spa, coa, and coa-RFLP in addition to toxin gene profiles. Most of the analyzed strains (40/50, 80%) were multidrug resistant (MDR), belonged to SCCmec-III, agr-I, and coa genotype I, and harbored sea and pvl genes. A negative correlation between the toxin gene profiles and antimicrobial resistance was recorded. Meanwhile, the correlation between the toxin gene profiles and the genetic background was not observed in this study. Although ST239-MRSA strains belonged to a single sequence type, they exhibited a high degree of phenotypic and genotypic diversity, indicating weak clonality and adaptability. With such diversity, it is assumed that these strains may have undergone different evolutionary processes during transmission events among and/or within a single host or tissue niche.

Whole-Genome Sequencing of Gram-Negative Bacteria Isolated From Bovine Mastitis and Raw Milk: The First Emergence of Colistin mcr-10 and Fosfomycin fosA5 Resistance Genes in Klebsiella pneumoniae in Middle East.

Antimicrobial resistance is a major concern in the dairy industry. This study investigated the prevalence, antimicrobial resistance phenotypes, and genome sequencing of Gram-negative bacteria isolated from clinical (n = 350) and subclinical (n = 95) bovine mastitis, and raw unpasteurized milk (n = 125). Klebsiella pneumoniae, Aeromonas hydrophila, Enterobacter cloacae (100% each), Escherichia coli (87.78%), and Proteus mirabilis (69.7%) were the most prevalent multidrug-resistant (MDR) species. Extensive drug-resistance (XDR) phenotype was found in P. mirabilis (30.30%) and E. coli (3.33%) isolates. Ten isolates (four E. coli, three Klebsiella species and three P. mirabilis) that displayed the highest multiple antibiotic resistance (MAR) indices (0.54-0.83), were exposed to whole-genome sequencing (WGS). Two multilocus sequence types (MLST): ST2165 and ST7624 were identified among the sequenced E. coli isolates. Three E. coli isolates (two from clinical mastitis and one from raw milk) belonging to ST2165 showed similar profile of plasmid replicon types: IncFIA, IncFIB, IncFII, and IncQ1 with an exception to an isolate that contained IncR, whereas E. coli ST7624 showed a different plasmid profile including IncHI2, IncHI2A, IncI1α, and IncFII replicon types. ResFinder findings revealed the presence of plasmid-mediated colistin mcr-10 and fosfomycin fosA5 resistance genes in a K. pneumoniae (K1) isolate from bovine milk. Sequence analysis of the reconstructed mcr-10 plasmid from WGS of K1 isolate, showed that mcr-10 gene was bracketed by xerC and insertion sequence IS26 on an IncFIB plasmid. Phylogenetic analysis revealed that K1 isolate existed in a clade including mcr-10-harboring isolates from human and environment with different STs and countries [United Kingdom (ST788), Australia (ST323), Malawi (ST2144), Myanmar (ST705), and Laos (ST2355)]. This study reports the first emergence of K. pneumoniae co-harboring mcr-10 and fosA5 genes from bovine milk in the Middle East, which constitutes a public health threat and heralds the penetration of the last-resort antibiotics. Hence, prudent use of antibiotics in both humans and animals and antimicrobial surveillance plans are urgently required.

Biocomputational Prediction Approach Targeting FimH by Natural SGLT2 Inhibitors: A Possible Way to Overcome the Uropathogenic Effect of SGLT2 Inhibitor Drugs.

The Food and Drug Administration (FDA) approved a new class of anti-diabetic medication (a sodium-glucose co-transporter 2 (SGLT2) inhibitor) in 2013. However, SGLT2 inhibitor drugs are under evaluation due to their associative side effects, such as urinary tract and genital infection, urinary discomfort, diabetic ketosis, and kidney problems. Even clinicians have difficulty in recommending it to diabetic patients due to the increased probability of urinary tract infection. In our study, we selected natural SGLT2 inhibitors, namely acerogenin B, formononetin, (-)-kurarinone, (+)-pteryxin, and quinidine, to explore their potential against an emerging uropathogenic bacterial therapeutic target, i.e., FimH. FimH plays a critical role in the colonization of uropathogenic bacteria on the urinary tract surface. Thus, FimH antagonists show promising effects against uropathogenic bacterial strains via their targeting of FimH's adherence mechanism with less chance of resistance. The molecular docking results showed that, among natural SGLT2 inhibitors, formononetin, (+)-pteryxin, and quinidine have a strong interaction with FimH proteins, with binding energy (∆G) and inhibition constant (ki) values of -5.65 kcal/mol and 71.95 µM, -5.50 kcal/mol and 92.97 µM, and -5.70 kcal/mol and 66.40 µM, respectively. These interactions were better than those of the positive control heptyl α-d-mannopyranoside and far better than those of the SGLT2 inhibitor drug canagliflozin. Furthermore, a 50 ns molecular dynamics simulation was conducted to optimize the interaction, and the resulting complexes were found to be stable. Physicochemical property assessments predicted little toxicity and good drug-likeness properties for these three compounds. Therefore, formononetin, (+)-pteryxin, and quinidine can be proposed as promising SGLT2 inhibitors drugs, with add-on FimH inhibition potential that might reduce the probability of uropathogenic side effects.

Effects of using Antifungal Gel on Retentive Bond Strength of Two Forms of Denture Adhesives: An in vitro Study.

AIM: The purpose of this in vitro study is to compare the bond strength to denture acrylics efficacy of miconazole gel against two denture adhesives with improved retentive properties (zinc-free PoliGrip cream and Snug denture soft cushion). MATERIALS AND METHODS: Eight heat-cured acrylic samples were prepared measuring 0.7 cm × 1.4 cm flat tested surface. The two well-adapted tested surfaces were matched and fixed to Universal Testing Machine clamp. Vertical separating load was applied at a rate of 1 mm/min to yield the maximum load before denture adhesive failure occurs. These measurements were used to express the retention bond strength when improved denture adhesive material was applied alone in comparison with micon-azole nitrate gel. Results were analyzed using one-way analysis of variance (ANOVA) statistical analysis at p-value of < 0.05. RESULTS: There was a statistically significant reduction in the mean tensile strength when the antifungal gel was opposed by the zinc-free PoliGrip cream. However, such a significant difference was not evident when the Snug denture cushion was opposed by the miconazole gel. CONCLUSION: The addition of antifungal gel to denture adhesives reduces retentive bond strength of denture adhesives to denture acrylics. However, if an antifungal gel has to be used, then a denture adhesive cushion soft plastic liner may provide a better retentive option than denture adhesive cream. CLINICAL SIGNIFICANCE: The incorporation of an antifungal agent into denture adhesives is required in many denture patients to suppress fugal growth and eliminate the undesirable health effects associated with such infections.

Seroprevalence of Toxoplasma gondii in women in Najran City, Saudi Arabia.

OBJECTIVES: To evaluate the seroprevalence of Toxoplasma gondii among Saudi pregnant women in Najran City, as well as to measure the performance of the diagnostic tests used. METHODS: A total of 96 women attending prenatal special clinics (Oteafyn special clinic) in Najran Province, Saudi Arabia, over a one year period, from September 2012 to September 2013 were screened for the presence of Toxoplasma antibody in their blood serum using an indirect hemagglutination assay (IHA). Specific immunoglobulin (Ig) G and IgM antibodies were evaluated using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Out of the 96 samples of sera tested using IHA, 20 (20.8%) were found to be positive with a titer ranging from 1:80 to 1:320, while 29 (29.2%) and 3 (3.1%) revealed Toxoplasma IgG and Toxoplasma IgM. A positive relationship was found between the seroprevalence of toxoplasmosis and age of tested women, especially in the age group of 21-30 years old (54.7%) by using ELISA-IgG, and 31-40 years old (4.5%) by using ELISA-IgM. CONCLUSION: The seroprevalence of Toxoplasmosis among pregnant women was found to be comparatively high, compared with previous reports from Saudi Arabia. Serologic checkup before and during pregnancy for seronegative women is recommended.

First national survey of Mycobacterium tuberculosis drug resistance, Madagascar, 2005-2006.

SETTING: A national survey of Mycobacterium tuberculosis resistance was conducted for the first time in Madagascar between October 2005 and July 2007. OBJECTIVE: To determine resistance rates among new and previously treated cases of pulmonary tuberculosis. METHODS: In a cluster sampling representative of the general population of the country, 1275 smear-positive tuberculosis patients recruited at 34 sites, 926 new patients and 87 previously treated patients underwent drug susceptibility testing against rifampicin (RMP), isoniazid (INH), streptomycin and ethambutol on Löwenstein-Jensen medium using the indirect proportion method. RESULTS: Resistance among new cases was 6.5% (95%CI 4.9-8) and among previously treated cases it was 11.5% (95%CI 4.8-18.2). Monoresistance among new cases was 5.8% (95%CI 4.2-7.3), mainly to INH (3.7%). Multiresistance to INH and RMP was 0.2% (95%CI 0-0.5) among new cases and 3.4% (95%CI 0-7.2) among previously treated cases. No significant difference was noted with regard to sex or age. CONCLUSION: The rates of resistance among new and previously treated cases remain relatively low in Madagascar.

Pyelovenous fistula: an uncommon cause of 'essential haematuria'.

Haematuria from obscure lesions of the kidney sometimes pose both diagnostic and therapeutic challenge. Recently, we managed a patient in whom a confident diagnosis of pyelovenous fistula was made.

Distribution and photodynamic effect of zinc phthalocyanine disulfonate in nude mice bearing mammary carcinoma.

The distribution study of zinc phthalocyanine disulfonate (ZnPcS2) in nude mice bearing mammary carcinoma (T50/80) revealed a rapid uptake of the dye by tumor. In experimental photodynamic therapy (PDT), the tumors were exposed to laser radiation (670 nm, 100 mW/cm2, 150 J/ /cm2) after intravenous administration of ZnPcS2 in saline. The results showed the maximum tumor destruction to be achieved for the time interval between injection of the drug (2 mg/kg) and exposure to laser light of 5 min, while a significantly less damage was observed when the time interval was 24 h (p < 0.0001). The degree of damage produced by the treatment was monitored in vivo by means of noninvasive NMR-imaging and subsequently confirmed histologically.