Multiple Drug Resistant Pathogens Research Articles

Novel Penicillin Derivatives Against Selected Multiple-drug Resistant Bacterial Strains: Design, Synthesis, Structural Analysis, In Silico and In Vitro Studies.

The rising numbers of multiple drug-resistant (MDR) pathogens and the consequent antibacterial therapy failure that resulted in severe medical conditions push to illustrate new molecules with extended activity against the resistant strains. In this manner, chemical derivatization of known antibiotics is proposed to save efforts in drug discovery, and penicillins serve as an ideal in this regard. Seven synthesized 6-aminopenicillanic acid-imine derivatives (2a-g) were structure elucidated using FT-IR, 1H NMR, 13C NMR, and MS spectroscopy. In silico molecular docking and ADMET studies were made. The analyzed compounds obeyed Lipinski's rule of five and showed promising in vitro bactericidal potential when assayed against E. coli, E. cloacae, P. aeruginosa, S. aureus, and A. baumannii. MDR strains using disc diffusion and microplate dilution techniques. The MIC values were 8 to 32 μg/mL with more potency than ampicillin, explained by better membrane penetration and more ligand-protein binding capacity. The 2g entity was active against E. coli. This study was designed to find new active penicillin derivatives against MDR pathogens. The products showed antibacterial activity against selected MDR species and good PHK, PHD properties, and low predicted toxicity, offering them as future candidates that require further preclinical assays.

Effect of intra-uterine administration of Lactobacillus bacteria on the steroid hormone profile in sub-clinical endometritis affected cows

Infertility in bovines is a major cause of serious economic loss to the dairy farmers. A major reason for infertility is sub-clinical, retrograde uterine infections. Sub-clinical endometritis is endometrial inflammation without apparent clinical manifestation and usually without signs of infection. This condition may be due to uterine infections or an extended inflammatory period that exists after elimination of bacteria. At present, infertility treatment is mainly done with intrauterine antibacterials, antiseptics and less commonly by hormones. These days, the major problem faced by animal reproductive health workers is the multiple drug resistance pathogens because of the indiscriminate use of antibiotics.Therefore, a different approach for more effective treatment of subclinical endometritis with Lactobacilli and its role on the steroid hormone profile was studied. In the present study, estradiol-17 β values were lower in the sub-clinical endometritis affected cows. Whereas, intra-uterine administration of Lactobacillus bacteria caused significant increase in estradiol level in a cycle after treatment in cross- bred cows. Similarly, the circulating serum progesterone concentration was also found to be low in subclinical endometritis affected cows. These findings could be used for clinical and experimental interpretations. Further, the information on pulsatile release of gonadotropins and steroid hormones status, receptors and its control, the close relationship among hormones could be necessary for better understanding of the role of steroid hormones in sub-clinical uterine infections.

Efficient biogenesis of calcium oxide nanoparticles using the extract of Eleusine coracana seeds and their application against multidrug-resistant ocular bacterial pathogens

Visual impairment due to corneal keratitis-causing bacteria is becoming a matter of health concern. The bacterial colonization and their resistance to multiple drugs need imperative attention. To overcome the issue of alternative remedial therapeutic agents, particularly for topical application, a study was carried out to synthesize calcium oxide nanoparticles (CaO NPs) using the biomaterial Eleusine coracana seed aqueous extract. The biosynthesized calcium oxide nanoparticles (CaO NPs) are non-toxic or less-toxic chemical precursors. Moreover, CaO NPs are eco-friendly and are used for several industrial, biomedical, and environmental applications. Biosynthesized CaO NPs were characterized using ultraviolet–visible spectroscopy, Fourier transform-infrared spectroscopy, scanning electron microscopy, and dynamic light scattering study. The synthesized CaO NPs exhibit with good anti-inflammatory activities with dose dependant (50–250 μg/mL). Moreover, Eleusine coracana-mediated CaO NPs significantly inhibited the multiple drug-resistant Gram-positive Staphylococci epidermidis and Enterococcus faecalis and Gram-negative Escherichia coli and Klebsiella pneumoniae that were isolated from the corneal ulcer. This study provides a potential therapeutic option for multiple drug-resistant corneal pathogens that cause vision impairment.

Evolutionarily conserved heat shock protein, HtpX, as an adjunct target against antibiotic-resistant Neisseria gonorrhoeae.

The emergence of multiple drug resistance and extreme drug resistance pathogens necessitates the continuous evaluation of the pathogenic genome to identify conserved molecular targets and their respective inhibitors. In this study, we mapped the global mutational landscape of Neisseria gonorrhoeae (an intracellular pathogen notoriously known to cause the sexually transmitted disease gonorrhoea). We identified highly variable amino acid positions in the antibiotic target genes like the penA, ponA, 23s rRNA, rpoB, gyrA, parC, mtrR and porB. Some variations are directly reported to confer resistance to the currently used front-line drugs like ceftriaxone, cefixime, azithromycinand ciprofloxacin. Further, by whole genome comparison and Shannon entropy analysis, we identified a completely conserved protein HtpX in the drug-resistant as well as susceptible isolates of N. gonorrhoeae (NgHtpX). Comparison with the only available information of Escherichia coli HtpX suggested it to be a transmembrane metalloprotease having a role in stress response. The critical zinc-binding residue of NgHtpX was mapped to E141. By applying composite high throughput screening followed by MD simulations, we identified pemirolast and thalidomide as high-energy binding ligands of NgHtpX. Following cloning and expression of the purified metal-binding domain of NgHtpX (NgHtpXd), its Zn2+ -binding (Kd = 0.4 µM) and drug-binding (pemirolast, Kd = 3.47 µM; and thalidomide, Kd = 1.04 µM) potentials were determined using in-vitro fluorescence quenching experiment. When tested on N. gonorrhoeae cultures, both the ligands imposed a dose-dependent reduction in viability. Overall, our results provide high entropy positions in the targets of presently used antibiotics, which can be further explored to understand the AMR mechanism. Additionally, HtpX and its specific inhibitors identified can be utilised effectively in managing gonococcal infections.

Unveiling the antibacterial potential and antibiotic-resistance breaker activity of Syzygium jambos (Myrtaceae) towards critical-class priority pathogen Klebsiella isolates

Background: Klebsiella has developed multiple-drug resistance (MDR) to a wide range of medicines, including carbapenems and third generation cephalosporins which are often regarded as the most effective drugs against MDR bacteria. The present study examined the anti-klebsiella, modes of action, and antibiotic-resistance reversal potential of Syzygium jambos (Myrtaceae) leaf (SJL) and bark (SJB) methanol extracts towards a panel of sixteen MDR K. pneumoniae and K. oxytoca strains and clinical isolates. Methods: The anti-klebsiella potential of SJL and SJB was assessed by determining the minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) using broth microdilution. Extracts were tested alone, in combination with an efflux pump inhibitor (PaβN), and in association with conventional antibiotics at their sub-inhibitory concentrations. Effects of SJL were also evaluated on bacterial kinetic growth, H+-ATPase-mediated pump, and cell membrane integrity, using standards. Results: SJL and SJB were shown to have anti-klebsiella action, with MICs ranging from 64 to 2048 g/mL. SJL was found to be more effective, acting on all tested pathogens with 100 ≤ MIC ≤ 2048 µg/mL, indicating considerable to moderate activity and generating bactericidal effects on more than half of the MDR Klebsiella strains investigated. SJL also produced a remarkably active effect (MIC ≤ 100 µg/mL), with MIC of 64 µg/mL against K. pneumoniae KP26. In the presence of PaβN, SJL and SJB activity rose significantly, demonstrating the involvement of active efflux machinery as MDR mechanisms. SJL displayed significant MDR reversal potential, as evidenced by an enhanced efficacy of conventional antibiotics, when in association. The activity of doxycycline and levofloxacin was improved on 100% of studied MDR pathogens. Interestingly, SJL also significantly enhanced the efficacy of the last resort drugs cefixime (cephalosporin) and imipenem (carbapenems) at more than 75% at MIC/2. Exposure of K. pneumoniae KP63 to SJL at 0.5×MIC, MIC, and 2×MIC for 20 h produced a concentration-dependent trend toward greater bacterial killing, extending the latent phase. In addition, SJL showed pronounced inhibition of the H+-ATPase-mediated pump and mildly disrupted the cytoplasmic membrane. Conclusion: This work provides a solid experimental foundation for considering S. jambos leaf extract as a viable treatment option for MDR Klebsiella-related illnesses. Keywords: Antibiotic-resistance modifying agents; efflux pump inhibitor; food plants; Klebsiella infections; multidrug resistance; Syzygium jambos.

Antimicrobial Activity of Biogenic Metal Oxide Nanoparticles and Their Synergistic Effect on Clinical Pathogens.

The rising prevalence of antibiotic-resistance is currently a grave issue; hence, novel antimicrobial agents are being explored and developed to address infections resulting from multiple drug-resistant pathogens. Biogenic CuO, ZnO, and WO3 nanoparticles can be considered as such agents. Clinical isolates of E. coli, S. aureus, methicillin-resistant S. aureus (MRSA), and Candida albicans from oral and vaginal samples were treated with single and combination metal nanoparticles incubated under dark and light conditions to understand the synergistic effect of the nanoparticles and their photocatalytic antimicrobial activity. Biogenic CuO and ZnO nanoparticles exhibited significant antimicrobial effects under dark incubation which did not alter on photoactivation. However, photoactivated WO3 nanoparticles significantly reduced the number of viable cells by 75% for all the test organisms, thus proving to be a promising antimicrobial agent. Combinations of CuO, ZnO, and WO3 nanoparticles demonstrated synergistic action as a significant increase in their antimicrobial property (>90%) was observed compared to the action of single elemental nanoparticles. The mechanism of the antimicrobial action of metal nanoparticles both in combination and in isolation was assessed with respect to lipid peroxidation due to ROS (reactive oxygen species) generation by measuring malondialdehyde (MDA) production, and the damage to cell integrity using live/dead staining and quantitating with the use of flow cytometry and fluorescence microscopy.

Unintended impact of COVID-19 pandemic on the rate of catheter related nosocomial infections and incidence of multiple drug resistance pathogens in three intensive care units not allocated to COVID-19 patients in a large teaching hospital

BackgroundThe prevalence of resistant hospital infections in the intensive care unit (ICU) increases mortality and antibiotic resistance. COVID-19 pandemic may have unintended impact on nosocomial infections (NI) and the prevalence of resistant microorganism.MethodologyThe present non-interventional study was performed by a pre and a post survey each lasting 8 months before (March–October 2019) and after (March–October 2020) the onset of COVID-19 pandemic in three ICU’s, not allocated to COVID-19 patients, in Nemazee Hospital, Shiraz, Iran. The rates of the following nosocomial infections were compared at pre- and post-pandemic period: ventilator associated pneumonia (VAP), central line associated blood stream infection (CLABSI), catheter-associated urinary tract infections (CAUTI) and incidence of multiple drug resistance (MDR) pathogens.ResultsPre-pandemic and pandemic incidence of VAP was 23.5 and 17.2 cases per 1000 device-days, respectively; an absolute decrease of 27%. The main reason for the decrease in the rate of VAP during the pandemic was a significant decrease in the rate of VAP caused by Acinetobacter baumannii; from 39 to 17% in total VAP episodes. The rate of VAP associated with other microorganisms remained relatively unchanged from 14.2 cases in pre-pandemic period to 14.3 cases per 1000 MV-days during the pandemic (P = 0.801). Pre-pandemic incidence of CLABSI was 7.3 cases and, in pandemic period, was 6.5 cases per 1000 device-days (IRR = 0.88, 95% CI 0.43–1.73, P = 0.703). Pre-pandemic incidence of CAUTI was 2 and in pandemic period, was 1.4 cases per 1000 device-days (IRR = 0.70, 95% CI 0.22–1.98, P = 0.469).ConclusionThe results of the present study showed a decrease in the incidence of VAP in critically ill non-COVID-19 patients during the pandemic compared to before the pandemic, especially regarding Acinetobacter baumannii.

Combined Effect of Isolated Bacteriophage and Neem Extract on Isolated Multiple Drug-Resistant Pathogenic Escherichia coli E1 From Well Water.

Multiple drug-resistant Escherichia coli (E. coli) is a serious cause of concern, and they can be observed in hospital settings, natural environment, and animals. Dissemination of multiple drug-resistant (MDR) E. coli can pose a high risk to public health. Moreover, they are hard to control with commercial antibiotics, since they have acquired resistance against most of them. Therefore, to control multiple drug-resistant bacteria, alternative strategies have been adopted such as phage therapy, herbal remedies, nanoparticles etc. In the current study, the combined application of neem leaf extract and bacteriophage is used to control an isolated multiple drug-resistant E. coli E1. We have applied 0.1 mg/ml concentration of neem extract in combination with an isolated phage vB_EcoM_C2 of 1011 titer and found that the combinatorial treatment approach significantly controls the growth of E. coli E1 as compared to a single non-combinatorial treatment. In this study, every E. coli cell is targeted by 2 antimicrobials (phage and neem extract) at the same time, which is more effective as compared to the sole treatment. Implementation of the neem extract with phage opens a new alternative approach to the chemotherapeutics for the control of multiple drug-resistant bacterial pathogens. This approach may be effective, economical, and eco-friendly to combat MDR.

CASE SERIES OF EMERGING NOSOCOMIAL MULTIPLE DRUG RESISTANT PATHOGEN PROVIDENCIA RETTGERI CAUSING URINARY TRACT INFECTION

We report Case Series of Emerging Nosocomial Multiple Drug Resistant Pathogen Providencia rettgeri causing Urinary Tract Infections. The most common cause of catheter-associated urinary tract infections (CAUTI), especially with long-term indwelling urinary catheters in elders, are P. rettgeri and P. stuartii. We are reporting 4 cases of UTI, which are hospital-acquired and CAUTI. These cases are admitted to MICU for treatment purposes and later develop fever spikes after a few days and are evaluated and urine culture showed multi-drug-resistant Providencia rettgeri by VITEK. The empirical therapy was discontinued, managed with fosfomycin, and discharged later with follow-up. The various reports showed P. rettgeriis susceptible for amikacin, gentamicin, tobramycin and ciprofloxacin. In our case series, we isolated multi-drug-resistant strains of P. rettgeri that showed resistance to piperacillin-tazobactam, cefuroxime, ceftriaxone, cefepime, ertapenem, imipenem, meropenem, gentamicin, tobramycin, ciprofloxacin, tigecycline, amikacin, colistin and sensitive only to fosfomycin. The significance of P. rettgeri in association with catheter-related bloodstream infections (CRBSI) and catheter-associated urinary tract infections (CAUTI) was unclear. Hence isolation of Providencia species twice from the clinical samples was considered for association with catheter infections. The proper selection of empirical antimicrobials, antibiotic sensitivity testing, avoiding misuse of antibiotics and implementing proper drug holiday and local antibiotic policy are considered appropriate combination protocol for managing emerging multi-drug-resistant nosocomial Providencia rettgeri strains.

Etiologies and antibiotic resistance patterns of acute bloodstream infections by gram-negative bacterial isolates in a tertiary care hospital, Sirajganj, Bangladesh

Bloodstream infections (BSI) are serious, life-threatening, and critical clinical conditions with high global human morbidity and mortality rates. This study aimed to determine the Gram-negative bacterial profiles and antimicrobial resistance patterns of acute bloodstream infections in rural patients. Three hundred forty-six blood samples were collected and analyzed with the BD BactecTM FX40 automated culture system, selective media culture, and biochemical parameters. Finally, antimicrobial susceptibility testing was performed using the disk diffusion method. The most common age group affected out of 51 cases was 41-60 years, with 20 patients (39.22%), and 1-15 years, with 2 patients (3.92%). Male patients were more susceptible (66.67%) than female patients. Among the isolates, E. coli was the most common, with 23 cases (45.1%); Cephradine was the most resistant antibiotic, and Imipenem was the most sensitive. Multiple drug-resistant pathogens were one of the most notable findings in our work. Our study will surely provide the best guide for properly treating antibacterial-resistant bacterial diseases and minimizing their critical mortality and morbidity. J. Bangladesh Acad. Sci. 46(2); 185-191: December 2022

Evaluation of the Simultaneous Effects of Lactobacillus delbrueckii and L. lactis on Biofilms of Isolates from Chronic Ulcer Infections with Multiple-drug Resistance

Background: Bacterial biofilm is a major barrier to chronic wound healing. Therefore, the prevention of biofilm formation has an effective role in accelerating the healing of these wounds. Today, probiotics' anti-biofilm and antibacterial activity have been proven, and bacteriotherapy by probiotics is a new strategy for treating chronic ulcer infections. Objectives: The present study aimed to investigate the synergistic effects of L. delbrueckii and L. lactis on biofilms of bacterial agents isolated from these ulcers in the human plasma biofilm model (hpBIOM). Methods: This study examined 82 specimens of chronic ulcer biofilms and identified bacterial isolates using phenotypic and molecular methods. After preparing the hpBIOM, 50 µL of each probiotic (109 CFU/mL) was added in two doses separately and simultaneously. After 24 hours, 1 mL of bromelain (0.1 g/mL) was added to the complex and incubated at 37°C for two hours. Then, the surviving bacterial cells were counted by serial dilutions. Results: Among 119 bacterial isolates, Staphylococcus aureus (19%), Escherichia coli (17.0%), and Pseudomonas aeruginosa (14%) were the most common bacterial isolates. Lactobacillus delbrueckii showed anti-biofilm activity against multiple-drug resistance pathogens, Staphylococcus, P. aeruginosa, and Klebsiella pneumoniae. Although L. lactis had anti-biofilm activity against these three pathogens, its effect was less than that of L. delbrueckii. The two probiotics did not have any synergistic effect on the biofilms of the isolates. Conclusions: The results of the present study emphasized the potential of probiotics in destroying biofilms of isolates with multiple-drug resistance; however, their simultaneous use for this purpose requires further investigation.

The Distribution Pattern of Acinetobacter baumannii Isolated from Two Tertiary Health Institutions in Rivers State, Nigeria

The ubiquitous nature of Acinetobacter baumannii has made the Gram-negative, non-motile bacterium to be associated with hospital-acquired infection at the global level, and with respect to antimicrobial resistance, it has been categorized among the most dangerous multiple drug-resistant (MDR) pathogens globally and enlisted in the "priority 1: critical" pathogens list of the World Health Organization, existing in-hospital patients and environment. Many clinical manifestations such as pneumonia, and wound infection have posed a huge disease burden with massive economic loss. The infection is associated with high morbidity and mortality rates. The burden of this hospital pathogen demands attention, especially with the surge in the resistant strains distribution. In the area of this study, distribution patterns have not extensively been studied therefore, the research focused on the distribution pattern of hospital isolated Acinetobacter baumannii from selected tertiary health facilities in Rivers State Nigeria. The observational study involved isolation and biochemical identification, as well as molecular assay, which was performed using standardized methods, was conducted in two main tertiary hospitals located in Port Harcourt metropolis, Rivers State, Nigeria. Statistics were performed for percentage and frequency distribution. Kruskal-Wallis and Mann-Whitney tests were used to compare the difference in distribution at a 0.05 level of significance. Statistical Package for Social Science version 21 was used for the statistics.368 samples from two institutions; RSUTH 185 (50.3%) and UPTH 183 (49.7%). Females 187 (50.8%) were more compared to the males 181(49.2%) with a significant difference (p<0.05) in isolate distribution but no statistically significant difference (p>0.05) for location and sample. Also, sample distribution was uneven 59 (16.0%), 202 (54.9%), and 107 (29.1%) for aspirate, urine, and wound respectively. 2.4% was recorded in the preliminary investigation while a 75% positive rate was observed using the molecular method. Evidence of the presence of Acinetobacter baumannii in the hospital was established. Also, Acinetobacter baumanii was not isolated from the aspirate sample however, this is subject to further investigation with an increased sample size. Female subjects had a higher rate. The information obtained here is essential to guide therapeutics and the management of targeted clinical manifestation. Therefore, the study serves as surveillance of A. baumannii found in the selected region.

English

This study was conducted to examine microbiological quality and antibiotic susceptibility of bacterial pathogen of ready to eat sliced pineapple and water melon. Pineapples and water melon were purchased from three different vendors in Sango, University of Ibadan and Apete markets. Isolation and identification of pathogens were carried out using culture dependent method, morphological and biochemical characterization, respectively. Bacterial isolates were tested for antibiotic susceptibility. Results showed that all samples were contaminated. Lactobacillus species had the highest percentage frequency of occurrence (35%), while Proteus, Pseudomonas, Shigella and Salmonella species had the least (5%). Multiple drug resistances were observed among the isolates when subjected to Ampicillin, Ceftazidine, Cefuroxine, and Augumentin. Despite the dominance of Lactobacillus spp. in this study, the presence of Escherichia coli, Shigella spp., and Salmonella spp., Staphylococcus aureus, Klebsiella pneumonia and Enterobacter species together with their multiple drug resistance call for public health attention. Quality of vended fruits will be better assured if there are improved hygienic practices and awareness among fruit vendors as well as the consumers. There is need to monitor the spread of multiple drug resistant antimicrobial pathogens in vended fruits to avoid outbreaks.   Key words: Microbiological quality, antibiotic susceptibility, multiple drug resistance ready to eat, pineapple, water melon.

Evaluation of In vitro Activity of Tigecycline against Multidrug-Resistant Clinical Isolates

Introduction: Multiple drug resistance (MDR) of the bacteria is an issue across any health-care setting worldwide. This leads to prolonged hospital stay and high cost of treatment. One must be cautious to use reserve drugs such as imipenem, meropenem, colistin, polymyxin, and tigecycline. Tigecycline is a mainstay to treat emerging single or MDR pathogens. The study was conducted to assess the in vitro sensitivity of tigecycline to MDR isolates and to compare the sensitivity of Kirby–Bauer (KB) disc-diffusion method with the Epsilometer (E-test) against various MDR clinical isolates. Materials and Methods: This prospective study was done from January 2019 to 2020 on MDR isolates from clinical specimens. The isolates were tested for their antibiotic sensitivity to tigecycline by KB and E-test method to know the minimum inhibitory concentration (MIC) of tigecycline. Statistical data were analyzed by the percentage method. Results: Tigecycline showed a higher in vitro sensitivity against multidrug-resistant isolates in our study. Among the 89 MDR isolates obtained, 38 (42.7) were found to be sensitive to tigecycline by the KB diffusion and 67 (75.3) were sensitive by the E-test method. Conclusions: Tigecycline is a reserve antibiotic against MDR organisms, especially useful to treat coinfections of Gram-positive and Gram-negative superbugs. The E-test was found to be far superior to the KB method to detect in vitro activity and the results of this test will guide the clinician to judiciously use this antibiotic in their day-to-day practice.

Time-Resolved Atomistic Imaging and Statistical Analysis of Daptomycin Oligomers with and without Calcium Ions.

Daptomycin (DP) is effective against multiple drug-resistant Gram-positive pathogens because of its distinct mechanism of action. An accepted mechanism includes Ca2+-triggered aggregation of the DP molecule to form oligomers. DP and its oligomers have so far defied structural analysis at a molecular level. We studied the ability of DP molecule to aggregate by itself in water, the effects of Ca2+ ions to promote the aggregation, and the connectivity of the DP molecules in the oligomers by the combined use of dynamic light scattering in water and atomic-resolution cinematographic imaging of DP molecules captured on a carbon nanotube on which the DP molecule is installed as a fishhook. We found that the DP molecule aggregates weakly into dimers, trimers, and tetramers in water, and strongly in the presence of calcium ions, and that the tetramer is the largest oligomer in homogeneous aqueous solution. The dimer remains as the major species, and we propose a face-to-face stacked structure based on dynamic imaging using millisecond and angstrom resolution transmission electron microscopy. The tetramer in its cyclic form is the largest oligomer observed, while the trimer forms in its linear form. The study has shown that the DP molecule has an intrinsic property of forming tetramers in water, which is enhanced by the presence of calcium ions. Such experimental structural information will serve as a platform for future drug design. The data also illustrate the utility of cinematographic recording for the study of self-organization processes.

Construction and Antibacterial Study of Targeted Peptide Nanodrug Delivery System

The discovery of broad-spectrum antibiotics has greatly reduced human mortality due to bacterial infections, but the widespread use of broad-spectrum antibiotics in the past 20 years has led to the emergence of multiple drug resistance (MDR) pathogens, making bacterial infection modern serious problems facing medicine. In addition, the abuse of broad-spectrum antibiotics can also cause diseases such as intestinal flora imbalance, colitis, and candidiasis. Therefore, it is of great significance to develop new targeted antibacterial drugs, which can effectively treat bacterial infections while reducing the generation of drug-resistant bacteria and avoiding the imbalance of microbiota in patients. Based on this, we designed a temperature-responsive nano-drug delivery system containing antimicrobial peptides. The system uses gold nanostars as carriers to couple targeted antimicrobial peptides and loads them into thermosensitive hydrogels. It can form a gel according to the increase in the ambient temperature, and the photothermal effect is stable. In vitro antibacterial experiments show that the system has an excellent killing ability for StaphylococcuS.aureus. The method reported in this article hopes to provide a certain reference value for future nanoparticle antibacterial research.

A Review on Microbial Products and Their Perspective Application as Antimicrobial Agents.

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and microalgae are an auspicious source of vital bioactive compounds. In this review, the existing research regarding antimicrobial molecules from microorganisms is summarized. The potential antimicrobial compounds from actinomycetes, particularly Streptomyces spp.; archaea; fungi including endophytic, filamentous, and marine-derived fungi, mushroom; and microalgae are briefly described. Furthermore, this review briefly summarizes bacteriocins, halocins, sulfolobicin, etc., that target multiple-drug resistant pathogens and considers next-generation antibiotics. This review highlights the possibility of using microorganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical applications. However, more investigations are required to isolate, separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

Synergistic effect of Silver and ZnO nanoparticles green synthesized by Vitis vinifera stem extract with Ampicillin against some pathogenic microbes

The increasing of multiple drug resistance pathogens necessitated extensive research for new safe and effective therapeutic agents. Vitis vinifera stem (VVS) hydroalcoholic extract beside its biosynthesized metallic nanoparticles silver (VVSAgNPs) and zinc oxide (VVSZnONPs) were tested against pathogenic microbes namely; B. subtilis ATCC6633, S. aureus ATCC29213, E. coli ATCC25922, S. typhimurium ATCC14028 and the fungus C. albicans ATCC1023.HPLC/MS/MS analysis of VVS extract led to identification of 31 compounds. The major compounds were malic, quinic and vanillic acids, catechin gallate and reservtrol and its dimer viniferin beside 11 fatty acid and terpene. The VVSAgNPs and VVSZnONPs were characterized using UV, FT-IR, TEM and zeta potential measurements. All the tested samples gave antimicrobial activity against all tested pathogens. VVSAgNPs were the most effective either alone or as synergists with the antibiotic ampicillin and giving the highest growth inhibition with the antibiotic at 1xMIC and 3xMIC. Also, the reduction of microbial population was more than 3 log for B. subtilis, E. coli and 2.3 log for C. albicans at 4xMIC using VVAgNPs. Vitis vinifera stem hydroalcoholic can be used in food industry and pharmaceutical industry as antimicrobial agent while silver nanoparticles could be used as a promising disinfectant with long stability on surface materials that could be used in the hospitals as a disinfectant spray for preventing emergence of microbial resistance.

Genome Dynamics and Evolution of Multiple-Drug-Resistant Bacteria: Implications for Global Infection Control Priorities.

Genomics-driven molecular epidemiology of pathogenic bacteria has largely been carried out through functionally neutral/inert sequences, mostly entailing polymorphic gene loci or repetitive tracts. However, it is very important to harness phenotypically relevant markers to assign a valid functional epidemiological context to tracking of pathogens. These should include microbial acumen to acquire multiple drug resistance (MDR), their physiological coordinates with reference to clinical or community-level dynamics of incidence/transmission, and their response or refractoriness to the activated immune system. We propose that multidimensional and multicentric approaches, based on diverse data integration coupled with comparative genomics and functional molecular infection epidemiology, would likely be successful in tracking the emergence and spread of MDR pathogens and thereby guiding the global infection control strategies in a highly informed manner.

Analisis of budget costs with different treatment efficiencies of newly diagnosed tuberculosis patients with multiple drug resistant pathogen

The article presents the results of predicting the dynamics of the spread of new cases of tuberculosis (TB) with multiple drug resistance (MDR) in the Republic of Karelia, as well as the costs of treating patients with tuberculosis, considering the different effectiveness of treatment. It has been demonstrated that while enhancing efficiency of treatment, due to the rapid determination of drug resistance by the method of polymerase chain reaction and a decrease in treatment gaps (using food kits), the effectiveness of treatment is significantly increased and the prevalence of MDR-TB decreases, which leads to significant budget savings.