STUDY OF THE ACUTE TOXICITY OF AQUADES-NUK PRODUCTS 5

In the system of veterinary and sanitary measures, disinfection occupies one of the important places, contributing to ensuring the welfare of animal husbandry against infectious diseases, increasing the productivity of animals, poultry and the sanitary quality of products, raw materials and animal feed. The main purpose of disinfection is to break the epizootic chain by influencing its most important link - the factor of transmission of the causative agent of the disease from the source of infection to the susceptible organism. Based on the foregoing, we were assigned the goal of studying the characteristics of the new domestic disinfectant AQUAdez-NUK 5, and to achieve this goal, one of the tasks was to study acute toxicity. In order to study the acute toxicity of AQUAdes-NUK 5 when administered orally, experiments were carried out on male Wister white rats weighing 220-230 g. at doses of 2000, 3000, 4000 and 5500 mg / kg. For the experiments, the rats were divided into groups of 10 animals. 10 animals were used to study each dosage for each disinfectant. One group of ten animals served as a control, which was injected with 0.9% sodium chloride solution. The disinfectant was injected in pure form. After administration, the laboratory animals were monitored for two weeks. The experiment took into account the death of animals and the clinical picture of intoxication. In the course of laboratory studies, we determined that AQUAdez-NUK 5 belongs to the III hazard class in accordance with GOST 12.1.007-76 (moderately hazardous compounds), as well as the presence of a weak irritant effect, and therefore we took appropriate safety measures during work with this disinfectant.

Clinical and Economic Burden of Bacteraemia Due To Multi-Drug-Resistant Organisms in Korea: A Prospectively Selected Case Control Study

BackgroundMultidrug-resistant organisms (MDROs), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug resistant Acinetobacter baumannii (MRAB), multidrug resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) are particularly important public health threats, but their detailed clinical outcomes and socioeconomic burden are adequately addressed.MethodsWe prospectively searched for these MDROs bacteraemia cases with matched controls from 10 hospitals across Korea, in a 6-month period, in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had similar principal diagnosis at admission time, major surgery or intervention during hospitalization, age (± 10 years), sex, and within ± 60 days of admission date. We collected detailed clinical information and estimated the total additional direct medical cost of each MDRO bacteraemia case using the multistate model. ResultsOf 486 MDRO bacteraemia cases identified for MRSA, MRAB, MRPA, CRE, and VRE, at 260, 87, 18, 20, and 101, respectively, their 90-day mortality rates (overall, 40.3%) were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. Their additional medical costs (overall, $27,700) were $15,768, $35,682, $39,908, $72,051, and $33,662 (compared to the no-infection group), respectively. Overall, these five MDRO bacteraemia cases occurred in 7,979 patients, caused 3,280 deaths, and cost $294,505,002 (range, $170,627,020 to $416,094,679) socioeconomic loss. ConclusionsTremendous clinical and economic burden occurred with MDRO bacteraemia compared with those of antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed to urgently prevent the increase, spread and expansion of antibiotic-resistant bacteria.

The main directions of non-specific prevention of infectious diseases

Infectious pathology continues to occupy one of the leading places in the structure of causes of death worldwide and in developing countries prevails over somatic. The most cost-effective way to prevent infectious diseases is vaccination. However, the use of vaccines cannot be implemented to combat all known infectious diseases, given their massive nature and often occurring polyetiology. In this regard, non-specific prevention is of particular relevance. In order to systematize and generalize the data of the scientific literature on methods and means of non-specific prevention, as well as to assess their effectiveness, a search for literary sources using electronic bibliographic resources was carried out https://pubmed.ncbi.nlm.nih.gov/ and https://elibrary.ru/ according to the keywords «non-specific prevention», «prevention of infections». The analysis of scientific works made it possible to evaluate non-specific prevention from the standpoint of classical epidemiology and the population approach to the organization of epidemiological studies and planning of preventive measures. The measures aimed at the source of infection, the mechanism of transmission and the susceptible organism in relation to different groups of infection are considered. Priority preventive and anti-epidemic measures were identified in relation to infections with aerosol, fecal-oral, contact and transmissible transmission mechanisms, and their effectiveness was evaluated. Special attention is paid to measures for the prevention of zoonotic and natural focal infections, as well as measures for the sanitary protection of the territory of the state from the import and spread of infectious diseases. The applicability of non-specific prevention of infectious morbidity in the conditions of the emergence of new biological threats is considered on the example of a new coronavirus infection COVID-19. It is established that the scientifically based tactics and methodology of non-specific prevention of infectious diseases are the property of domestic and world epidemiology, and its effectiveness has been tested by time and does not lose relevance today. The risk of new threats indicates that the improvement of this approach is a promising direction for the prevention of infectious diseases.

The Antimicrobial, Anti Inflammatory and Analgesic Activities of the Rhizome Extract of Curcuma longa L. (Turmeric)

Aim: This study aimed at investigating the anti-microbial, anti-inflammatory, and analgesic properties of rhizome extracts of Curcuma longa (Turmeric). Methodology: Extraction of biochemical constituents of the 150 g of the turmeric rhizomes powder was carried out successively using hexane, ethyl acetate, methanol, and water as solvents. The antimicrobial potentials of the different fractions of the extract were tested on clinical bacterial including Staphylococcus aureus, Streptococcus pneumonia, Klebsiella pneumonia and Pseudomonas aeruginosa using agar well diffusion method at concentrations of 400 mg/ml, 200 mg/ml, 100 mg/ml, 50 mg/ml, and 25 mg/ml. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined using agar dilution technique. For the anti-inflammatory effects of the extract of C. longa, albino rats were treated with methanolic extract (250, 500, and 1000 mg/kg body weight) and diclofenac as control, after which they were injected with egg albumin on the right hind paw to induce inflammation. The swelling degree of the injected paw was measured. The analgesic effect of C. longa methanolic extract on hot plate-induced pain was also investigated in albino rats, and the Index of response latency was recorded. Results: The biochemical assay showed that C. longa extract contained Alkaloids, Saponins, Tannins, Flavonoids, Carbohydrate, Steroids, Terpenes, Anthraquinone, and Cardiac Glycosides, with Methanol and aqueous extracts having the most biochemical constituents. The antibacterial susceptibility screening showed that K.pneumonia was the most susceptible organism, having the highest zone of inhibition of 18 mm for ethyl acetate extract at the concentration of 400 mg/ml. This was followed by S. pneumonia, S.aureus and P. aeruginosa with inhibition zone of 13, 12 and 10 mm respectively. The MIC for K.pneumonia and S.aureus were both 200 mg/ml, while that of P. aeruginosa and S. pneumonia were both 400 mg/ml. The paw size of rats treated with increasing doses of the extract and diclofenac significantly decreased with time. The concentration of 250 mg/kg had the lowest paw volume of 4.39±0.36mm while 1000 mg/kg recorded 5.18±0.28 as the highest, at 180 minute. Conclusion: Based on the result obtained, it can be concluded that Curcuma longa Rhizome extract possess anti-microbial, anti-inflammatory, and analgesic properties.

Microbial Sensing and Removal of Heavy Metals: Bioelectrochemical Detection and Removal of Chromium(VI) and Cadmium(II)

The presence of inorganic pollutants such as Cadmium(II) and Chromium(VI) could destroy our environment and ecosystem. To overcome this problem, much attention was directed to microbial technology, whereas some microorganisms could resist the toxic effects and decrease pollutants concentration while the microbial viability is sustained. Therefore, we built up a complementary strategy to study the biofilm formation of isolated strains under the stress of heavy metals. As target resistive organisms, Rhizobium-MAP7 and Rhodotorula ALT72 were identified. However, Pontoea agglumerans strains were exploited as the susceptible organism to the heavy metal exposure. Among the methods of sensing and analysis, bioelectrochemical measurements showed the most effective tools to study the susceptibility and resistivity to the heavy metals. The tested Rhizobium strain showed higher ability of removal of heavy metals and more resistive to metals ions since its cell viability was not strongly inhibited by the toxic metal ions over various concentrations. On the other hand, electrochemically active biofilm exhibited higher bioelectrochemical signals in presence of heavy metals ions. So by using the two strains, especially Rhizobium-MAP7, the detection and removal of heavy metals Cr(VI) and Cd(II) is highly supported and recommended.

MACROMICROSCOPIC ARGUMENTATION OF THE PATHOGENETIC SCENARIO OF BABESIOSIS IN THE COORDINATE SYSTEM «PATHOGEN-CARRIER-RESERVOIR»

The aim is to get a thorough argument for the babesiosis pathogenetic scenario in the coordinate system «pathogen (Babesia spp.) – carrier (ticks of the Ixodoidea superfamily of the Ixodidea family) – reservoir (a susceptible organism)» with the emphasis on the epizootic/epidemic role of the carrier. Materials and methods: The macromicroscopic method of research was used in order to maximize the clarification of the babesiosis scenario, its pathogenetic links, the connection of the latter with attacks of active stages of ixodes ticks, types of circulation of ontogenetic forms of Babesia spp. in the body of carriers and their inoculation of the pathogen into an organism susceptible to it. The use of this method helped to strengthen the diagnostic potential of the study, and increase the reliability of the results obtained. Taking this into consideration it was focused on the epizootological/epidemiological aspects of babesiosis, the role and significance of the most vulnerable epizootic link – Ixodes ticks on the body of the vertebrate provider (mammal), poikilomorphism, anisomorphy. The study of the monolithic idiosome and ticks salivary glands were carried out on activated (capable of attack) female individuals aged 2-3 months after molting. Ticks were dissected in a cool (t=4ºC) Ringer’s saline solution for arachnids. Ticks and prepared salivary glands were fixed in 12% formalin solution on 0.1 M phosphate buffer (pH=7.0-7.2) at t=4oC for 3 hours, washed with the buffer, and fixed again for 1 hour (t=4oC). To achieve tonicity, sucrose was added to the fixatives and the washing medium. Dehydration occurred due to a battery of alcohols of increasing concentration and absolute acetone. Microspecimens stained with hematoxylin and eosin were studied using an Olympus BX-41 microscope (Japan). Results: Implementation of the leading stages of the babesiosis pathogenetic scenario is focused on the coordinate system «pathogen (Babesia spp.) − carrier (ticks of the Ixodoidea superfamily of the Ixodidea family) − reservoir (a susceptible organism)» in which carrier take the leading place. The macromicroscopic specificity of the structure of the ticks (variability: ability to aniso-, poikilomorphism) is an evidence-based criterion for pathogens inoculation to the macroorganism of warm-blooded vertebrates. It determines the features of circulation and organ/cellular locations of Babesia spp. (intestines and its epithelium, hemolymph, gonads, salivary glands). The species belonging of warm blooded vertebrates susceptible to babesiosis pathogens correlates with the species belonging of ticks and determines the tropicity of the latter. The simultaneous implementation of a complex of research procedures with the tick biological material samples is problematic taking into account the physical lack of material, which requires researchers to re-orient the diagnostic vector towards the use of additional methods for babesiosis diagnosing, including in vitro ones. Conclusions: In the pathogenetic scenario of babesiosis, the carrier (Ixodes ticks) is the central figure in the epidemic/epizootic coordinate system.

Chemo-Diversity of Antibacterial Anthraquinones from the Roots of Morinda morindoides

Background: Morinda morindoides (Baker) (Rubiaceae) is a medicinal plant with antimicrobial properties currently used in Côte d'Ivoire and other countries. These properties have been described but most of the studies are dealing with crude extracts. Objective: The chemical structures of the bioactive compounds extracted from Morinda morindoides roots have been characterized. Methods: The root extracts were analyzed by using HPLC. Fourteen fractions were detected among which 11 compounds have been structurally identified by using a combination of 1H-NMR and 13CNMR and LC-HRMS methodologies. Results: All these compounds belong to anthraquinone family. The antibacterial activity of the eleven compounds was tested against six strains of microorganisms with ofloxacin as standard (two Gram-negative bacteria, two Gram-positive bacteria and two yeasts). The Minimal Inhibitory Concentrations recorded, varies from 8 to 128 μg / ml. Staphylococcus aureus was the most susceptible organism. Conclusion: We highlight the chemo-diversity of the antibacterial anthraquinones in the roots of Morinda morindoides.

2000. Utilization of a ‘Never Event’ Framework to Classify Antimicrobial Appropriateness

Background Contemporary strategies can be leveraged to predict antimicrobial overuse, yet little information is gained on the appropriateness of antibiotics prescribed. Classifying appropriateness is complicated by the lack of a standard definition for appropriateness. Thus, we created and implemented a novel ‘antibiotic never event’ (NE) framework to systematically classify the most inappropriate usages of vancomycin and correlated these NE to abnormal consumption trends (i.e., antibiotic outbreaks). Methods Vancomycin use was categorized by an algorithm using data query from the electronic medical records. Extracted data included vancomycin use, relevant patient demographics, and microbiological data. Electronic classifications placed each vancomycin therapy into type 1 (use for non-susceptible organism after susceptibility finalization) or type 2 (use exceeding 48h after susceptibility report when a safe de-escalation is possible) NE. Patients were categorized as cases or controls (no NE) at Northwestern Memorial Hospital (NM) and Henry Ford Hospital (HF) between January 2014 and October 2017. A manual chart review was performed. Sensitivity (SEN), specificity (SPEC), PPV, and NPV were calculated for NE prediction. Vancomycin use was quantified during the same period. Linear models with prediction intervals (PI) were generated to identify potential outbreaks, which were linked to monthly NE counts defined as a binary factor. Results A total of 220 NE cases were electronically identified for vancomycin at NM (n = 197) and HF (n = 23). Random cases were matched 1:1 (NM = 200) and 1:5 (HF = 115) to controls for manual review. At NM and HF, 35 and 24 true positives were identified, respectively. Thus, overall SEN and SPEC were 93.7% and 75.1% and PPV and NPV were 45.7% and 98.1%, respectively. Linear models revealed 11 potential outbreak periods at HF and 5 at NM. A PI of 80% showed a combined SEN below 10% and SPEC above 90%, respectively. Conclusion The methodology was generalizable across two centers. In the pilot review, our method was highly sensitive and an effective screening tool for NE identification. Antibiotic consumption trends did not correlate with NE. In summary, the NE classification was sensitive in assessment of antibiotic appropriateness, whereas consumption alone does not predict NE. Disclosures All authors: No reported disclosures.

Antibiotic usage promotes the evolution of resistance against gepotidacin, a novel multi-targeting drug

Multi-targeting antibiotics, i.e. single compounds capable to inhibit two or more bacterial targets offer a promising therapeutic strategy, but information on resistance evolution against such drugs is scarce. Gepotidacin is an antibiotic candidate that selectively inhibits both bacterial DNA gyrase and topoisomerase IV. In a susceptible organism, Klebsiella pneumoniae, a combination of two specific mutations in these target proteins provide an over 2000-fold increment in resistance, while individually none of these mutations affect resistance significantly. Alarmingly, gepotidacin-resistant strains are found to be as virulent as the wild-type K. pneumoniae strain in a murine model, and extensive cross-resistance was demonstrated between gepotidacin and ciprofloxacin, a fluoroquinolone antibiotic widely employed in clinical practice. This suggests that numerous fluoroquinolone-resistant pathogenic isolates carry mutations which would promote the evolution of clinically significant resistance against gepotidacin in the future. We conclude that prolonged antibiotic usage could select for mutations that serve as stepping-stones towards resistance against antimicrobial compounds still under development. More generally, our research indicates that even balanced multi-targeting antibiotics are prone to resistance evolution.

Outcome of Irrigation and Debridement after Failed Two-Stage Reimplantation for Periprosthetic Joint Infection

Introduction. Two-stage revision is the gold standard for the treatment of deep implant infection after knee or hip arthroplasty. Irrigation and debridement may be a treatment option for failed 2-stage revisions in cases where a reinfection occurs within 30 days or the symptoms exist not longer than 3 weeks and is appealing because of its low morbidity. We determined the incidence of recurrent infections following irrigation and debridement for failed two-stage revision hip and knee arthroplasty. Methods. We performed a single center retrospective review of periprosthetic hip and knee infections treated with a two-stage procedure from 2002 to 2010. All patients that subsequently underwent irrigation and debridement for a subsequent infection were selected for the current study. Results. 440 two-stage revisions were performed between 2002 and 2010. Fifty-one two-stage revisions failed (11.6%). Nineteen failed two-stage revisions were treated with irrigation and debridement; 12 (63.2%) patients remained free of infection at follow-up (mean follow-up: 39 months; range, 24-90 months), infection persisted in 6 patients (31.6%), and 1 patient died (5.3%). Conclusions. Success rates of irrigation and debridement for failed two-stage procedures are similar to the success rates of irrigation and debridement in primary implant infections. According to the current paper, irrigation and debridement are an acceptable treatment for acute reinfections after failed two-stage revision if performed within the first 30 postoperative days after failed two-stage procedure or if symptoms are present for less than 3 weeks in the presence of a susceptible organism.