Multidrug-resistant Bacterial Pathogens Research Articles

Endocytosis-mediated redistribution of antibiotics targets intracellular bacteria.

The increasing emergence and dissemination of antibiotic resistance pose a severe threat to overwhelming healthcare practices worldwide. The lack of new antibacterial drugs urgently calls for alternative therapeutic strategies to combat multidrug-resistant (MDR) bacterial pathogens, especially those that survive and replicate in host cells, causing relapse and recurrence of infections. Intracellular drug delivery is a direct efficient strategy to combat invasive pathogens by increasing the accumulation of antibiotics. However, the increased accumulation of antibiotics in the infected host cells does not mean high efficacy. The difficulty of treatment lies in the efficient intracellular delivery of antibiotics to the pathogen-containing compartments. Here, we first briefly review the survival mechanisms of intracellular bacteria to facilitate the exploration of potential antibacterial targets for precise delivery. Furthermore, we provide an overview of endocytosis-mediated drug delivery systems, including the biomedical and physicochemical properties modulating the endocytosis and intracellular redistribution of antibiotics. Lastly, we summarize the targets and payloads of recently described intracellular delivery systems and their modes of action against diverse pathogenic bacteria-associated infections. This overview of endocytosis-mediated redistribution of antibiotics sheds light on the development of novel delivery platforms and alternative strategies to combat intracellular bacterial pathogens.

Outer Membrane Vesicle-Coated Nanoparticle Vaccine Protects Against Acinetobacter baumannii Pneumonia and Sepsis.

The highly multidrug-resistant (MDR) Gram-negative bacterial pathogen Acinetobacter baumannii is a top global health priority where an effective vaccine could protect susceptible populations and limit resistance acquisition. Outer membrane vesicles (OMVs) shed from Gram-negative bacteria are enriched with virulence factors and membrane lipids but heterogeneous in size and cargo. We report a vaccine platform combining precise and replicable nanoparticle technology with immunogenic A. baumannii OMVs (Ab-OMVs). Gold nanoparticle cores coated with Ab-OMVs (Ab-NPs) induced robust IgG titers in rabbits that enhanced human neutrophil opsonophagocytic killing and passively protected against lethal A. baumannii sepsis in mice. Active Ab-NP immunization in mice protected against sepsis and pneumonia, accompanied by B cell recruitment to draining lymph nodes, activation of dendritic cell markers, improved splenic neutrophil responses, and mitigation of proinflammatory cytokine storm. Nanoparticles are an efficient and efficacious platform for OMV vaccine delivery against A. baumannii and perhaps other high-priority MDR pathogens.

Bicyclomycin Activity against Multidrug-Resistant Gram-Negative Pathogens.

The growing prevalence of antimicrobial resistance poses a grave threat to human health. Among the most difficult bacterial infections to treat are those caused by multidrug-resistant (MDR) Gram-negative pathogens because few effective regimens are available. One approach to this problem is to find ways to increase the activity of old antimicrobials that had seen limited application. Bicyclomycin, an inhibitor of transcription termination, is an example in which the additional inhibition of protein or RNA synthesis increases bicyclomycin-mediated lethality against Gram-negative bacteria. To examine the potential of bicyclomycin for the treatment of MDR bacterial pathogens, we first measured the MICs of bicyclomycin and other widely used antimicrobials against more than 100 multidrug-resistant Gram-negative clinical isolates. Bicyclomycin showed good coverage of carbapenem-resistant Enterobacteriaceae (CRE) and Escherichia coli (MIC50/MIC90 of 25/50 μg/mL for both bacteria) and moderate activity against Klebsiella pneumoniae (MIC50/MIC90 of 50/200 μg/mL). Bicyclomycin also exhibited synergy (e.g., fractional inhibitory concentration [FIC] index of <0.5) with doxycycline for the inhibition of bacterial growth by a checkerboard assay. Although bicyclomycin exhibited very weak lethality by itself, it showed synthetic lethality with doxycycline against K. pneumoniae: the combination killed 100- to 1,000-fold more bacteria than either agent alone. In a murine model of infection, the bicyclomycin-doxycycline combination showed better efficacy than either agent alone, and the combination treatment largely eliminated histopathological manifestations caused by infection. Thus, bicyclomycin, which has largely been limited to the treatment of Gram-negative digestive tract infections, can now be considered for the combination treatment of systemic multidrug-resistant infections caused by CRE, E. coli, and K. pneumoniae. IMPORTANCE As antimicrobial resistance continues to increase, options for effectively treating multidrug-resistant (MDR) Gram-negative infections are declining. Finding ways to enhance the lethality of old agents that have unique molecular targets is important because developing new antimicrobials is becoming increasingly difficult. The present work showed that the old antibiotic bicyclomycin has good bacteriostatic activity against multiple clinical isolates of three significant types of MDR Gram-negative pathogens frequently encountered in hospital infections, as required for the consideration of expanded indications. More significant is the synergistic growth-inhibitory effect and the enhancement of killing by the additional presence of doxycycline since this increases the in vivo efficacy. These data demonstrate that bicyclomycin-containing regimens have potential as new treatment options for MDR Gram-negative infections such as those caused by CRE, E. coli, and K. pneumoniae.

Demystifying Bacteriocins of Human Microbiota by Genome Guided Prospects: An Impetus to Rekindle the Antimicrobial Research.

The human microbiome is a reservoir of potential bacteriocins that can counteract multidrug resistant bacterial pathogens. Unlike antibiotics, bacteriocins selectively inhibit a spectrum of competent bacteria and are said to safeguard gut commensals, reducing the chance of dysbiosis. Bacteriocinogenic probiotics or bacteriocins of human origin will be more pertinent in human physiological conditions for therapeutic applications to act against invading pathogens. Recent advancement in the omics approach enables the mining of diverse and novel bacteriocins by identifying biosynthetic gene clusters from the human microbial genome, pangenome or shotgun metagenome, which is a breakthrough in the discovery line of novel bacteriocins. This review summarizes the most recent trends and therapeutic potential of bacteriocins of human microbial origin, the advancement in the in silico algorithms and databases in the discovery of novel bacteriocin, and how to bridge the gap between the discovery of bacteriocin genes from big datasets and their in vitro production. Besides, the later part of the review discussed the various impediments in their clinical applications and possible solution to bring them into the frontline therapeutics to control infections, thereby meeting the challenges of global antimicrobial resistance.

Antimicrobial Activity of Auranofin, Cannabidivarin, and Tolfenamic Acid against Multidrug-Resistant Neisseria gonorrhoeae.

Alternative antimicrobial therapies are urgently required for the multidrug-resistant bacterial pathogen Neisseria gonorrhoeae, for which currently ceftriaxone is the only remaining recommended first-line therapy. Repurposing of drugs that are approved for other clinical applications offers an efficient approach for development of alternative antimicrobial therapies. Auranofin, cannabidivarin, and tolfenamic acid were recently identified to display antimicrobial activity against N. gonorrhoeae. Here, we investigated their activity against a collection of 575 multidrug-resistant clinical isolates. All three compounds displayed consistent antimicrobial activity against all isolates, including against strains associated with the high-level ceftriaxone-resistant FC428 clone, with both the mode and MIC90 for auranofin of 0.5 mg/L, while both the mode and MIC90 for cannabidivarin and tolfenamic acid were 8 mg/L. Correlations between MICs of ceftriaxone and auranofin, cannabidivarin or tolfenamic acid were low, indicating that development of cross-resistance is unlikely. Furthermore, antimicrobial synergy analysis between ceftriaxone and auranofin, cannabidivarin, or tolfenamic acid by determination of the fractional inhibitory concentration index (FICI) resulted in an interpretation of indifference. Finally, time-kill analyses showed that all three compounds are bactericidal against both the N. gonorrhoeae ATCC 49226 reference strain and an FC428-associated clinical isolate, with particularly cannabidivarin displaying rapid bactericidal activity. Overall, auranofin, cannabidivarin, and tolfenamic acid displayed consistent antimicrobial activity against multidrug-resistant N. gonorrhoeae, warranting further exploration of their suitability as alternative antimicrobials for treatment of gonococcal infections. IMPORTANCE Neisseria gonorrhoeae is a major public health concern because of the high incidence of gonorrhea and the increasingly limited options for antimicrobial therapy. Strains associated with the FC428 clone are a particular concern because they have shown global dissemination and they display high-level resistance against the currently recommended ceftriaxone therapy. Therefore, development of alternative antimicrobial therapies is urgently required to ensure treatment of gonorrhea remains available in the future. Repurposing of clinically approved drugs could be a rapid approach for the development of such alternative antimicrobials. In this study, we showed that repurposing of auranofin, cannabidivarin, and tolfenamic acid for antimicrobial therapy of gonorrhea deserves further clinical explorations because these compounds displayed consistent antimicrobial activity against a large collection of contemporary multidrug-resistant gonococcal isolates that included strains associated with the FC428 clone.

Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant Staphylococcus aureus.

The discovery of new classes of antibiotics is slow, and it is being greatly outpaced by the development of bacterial resistance. This disparity places us in an increasingly vulnerable position because we are running out of safe and effective therapeutic options to treat antibiotic-resistant infections. This is exemplified by the emergence and persistence of hospital-acquired and community-associated methicillin-resistant S. aureus (MRSA), which has markedly narrowed our options for treating life-threatening staph infections. Thus, there is an urgent need to develop novel, potent, preventive, and therapeutic agents. In our current study, we performed a whole-cell screening assay of synthetic libraries for antibacterial activity and identified a novel molecule, MZ-01. MZ-01 exhibited potent bactericidal activity against Gram-positive bacterial pathogens, including MRSA, Streptococcus pyogenes, and Streptococcus pneumoniae, at low concentrations. MZ-01 killed and lysed both the late exponential phase of an S. aureus population and bacteria inside mammalian cells. Furthermore, MZ-01 exhibited low cytotoxicity. These results indicate that MZ-01 is a promising scaffold to guide the development of novel, potent antibacterial agents against multidrug-resistant Gram-positive bacterial pathogens such as MRSA.

Synthesis, Biocidal and Antibiofilm Activities of New Isatin-Quinoline Conjugates against Multidrug-Resistant Bacterial Pathogens along with Their In Silico Screening.

Isatin-quinoline conjugates 10a-f and 11a-f were assembled by the reaction of N-(bromobutyl) isatin derivatives 3a, b with aminoquinolines 6a-c and their corresponding hydrazinyl 9a-c in good yields. The structures of the resulting conjugates were established by spectroscopic tools and showed data consistent with the proposed structures. In vitro antibacterial activity against different bacterial strains was evaluated. All tested conjugates showed significant biocidal activity with lower MIC than the first line drugs chloramphenicol and ampicillin. Conjugates 10a, 10b and 10f displayed the most potent activity against all clinical isolates. The antibiofilm activity for all tested conjugates was screened against the reference drug vancomycin using the MRSA strain. The results revealed that all conjugates had an inhibitory activity against biofilm formation and conjugate. Conjugate 11a showed 83.60% inhibition at 10 mg/mL. In addition, TEM studies were used to prove the mechanism of antibacterial action of conjugates 10a and 11a against (MRSA). Modeling procedures were performed on 10a-f and 11a-f and interestingly the results were nearly consistent with the biological activities. In addition, in silico pharmacokinetic evaluation was performed and revealed that the synthesized compounds 10a-f and 11a-f were considered drug-like molecules with promising bioavailability and high GI absorption. The results confirmed that the title compounds caused the disruption of bacterial cell membranes and could be used as potential leads for the further development and optimization of antibacterial agents.

Green Synthesis of Zinc Oxide Nanocrystals Utilizing Origanum majorana Leaf Extract and Their Synergistic Patterns with Colistin against Multidrug-Resistant Bacterial Strains

There is a crucial necessity for the formulation of efficient antimicrobial agents owing to the increasing prevalence of hospital-acquired bacterial infections triggered by multidrug-resistant microbes that result in significant deaths and illnesses around the world. Hence, the current investigation examined the antibacterial proficiency of zinc oxide nanoparticles formulated utilizing the green route against bacterial strains that were resistant to multiple drugs. In addition, the synergistic antibacterial action of ZnO nanoparticles (ZnO NPs) combined with colistin was investigated against the tested microbial strains to determine the efficiency of the bioinspired ZnO nanoparticles in boosting the antibacterial proficiency of colistin antibiotic. Incidentally, the bioinspired ZnO nanoparticles were synthesized using water extract of Origanum majorana leaves and these nanomaterials were physicochemically characterized using different analytical techniques. The bioactivity of the synthesized nanomaterials against multidrug-resistant bacterial strains was appraised using the agar diffusion method. The biogenic ZnO NPs at a concentration of 100 μg/disk revealed a compelling antimicrobial efficacy against the tested strains, expressing the maximum antimicrobial action against Escherichia coli strain with clear zone diameter of 38.16 ± 0.18 mm. The remarkable antibacterial proficiency might be accredited to the tiny particle size of the bioformulated ZnO NPs of 12.467 ± 1.36 nm. The net charge of ZnO nanomaterials was −14.8 mV while XRD analysis confirmed their hexagonal wurtzite structure. Furthermore, the bioformulated ZnO NPs showed a promising synergistic potency with colistin demonstrating respective synergism proportions of 91.05, 79.07, 75.04, 75.25, 56.28 and 10.60% against E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, Salmonella typhimurium, Enterobacter cloacae, and Pseudomonas aeruginosa, respectively. In conclusion, the water extract of O. majorana leaves mediated green formulation of zinc oxide nanoparticles with unique physicochemical characteristics and effective antibacterial proficiency against the examined drug-resistant bacterial strains. These nanomaterials could be used in the synthesis of effective antibacterial coatings to control hospital acquired infections caused by multidrug-resistant bacterial pathogens.

Green synthesis of gold nanoparticles (AuNPs) using Caulerpa racemosa and evaluation of its antibacterial and cytotoxic activity against human lung cancer cell line

The present study reports the synthesis of gold nanoparticles (AuNPs) using ‘sea grapes’ (Macroalgae) of Caulerpa racemosa extract in a simple, fast and environmentally friendly biogenic method. The formation of spherical, stable, polycrystalline nanoparticles with an average size of 18–45 nm was demonstrated by UV–vis spectroscopy, SEM, high-resolution transmission electron microscopy and X-ray diffraction measurements. Furthermore, FTIR analysis confirmed the presence of phytochemical constituents in the form of functional groups involved in AuNPs synthesis. Antimicrobial activities confirmed that Gram-negative bacteria, here represented by Escherichia coli, were found to be more sensitive to synthesized AuNPs than Gram-positive bacteria, represented by Staphylococcus aureus. The synthesized nanoparticles also showed cytotoxicity against human lung cancer cells (H460) with an IC50 value of 25 µg/mL. Furthermore, our findings show that AuNPs derived from C. racemosa extract are able to induce apoptosis activation via extrinsic and intrinsic pathways and mitochondrial pathways. These findings lay the groundwork for future research against emerging multi-drug resistant bacterial pathogens, as well as lung cancer treatment.

IN VITRO TO IN VIVO: COMBATING MULTIDRUG-RESISTANT ENTEROBACTERIACAE IN THE AGE OF COVID-19

IN VITRO TO IN VIVO: COMBATING MULTIDRUG-RESISTANT ENTEROBACTERIACAE IN THE AGE OF COVID-19

GC-MS Analysis of Volatile Constituents, Antibacterial Activity, and Mechanism of Action of the Essential Oil from Cinnamomum Cassia Bark Against Vancomycin-Resistant Enterococci

Background &amp; Objectives: An alarming rise in multi-drug resistant bacterial pathogen like Vancomycin-resistant Enterococci (VRE) has culminated in a global health threat in today’s healthcare environment and has caused significant morbidity and mortality in patients. The field of medicinal herbs has developed at an exponential rate in subsequent decades. Acknowledging the antimicrobial mechanisms of essential oils and their components is vital for developing them as a potential new source of antibiotics that can work as an alternative treatment for multi-drug resistant bacterial infections. Methods: The current study investigates the physiochemical properties and a variety of analytical and biological activities to determine the activity of Cinnamomum cassia essential Oil against drug-resistant microorganisms by utilizing a Time kill curve and evaluating the Minimum Inhibitory Concentration (MIC) of oil. The antimicrobial properties were assessed using a growth curve and the cell membrane’s integrity. The essential oil was retrieved by hydro-distilling Cinnamon bark, and the volatile components of the essential oil were determined by Gas Chromatography-Mass Spectrometry (GC-MS). Result: GC-MS analysis detected major components such as Cinnamaldehyde-(E) (37.40%); 2-Propenal, 3-phenyl (11.70%) and 1,6-Octadien-3-ol,3,7- dimethyl- (5.97%). The minimum inhibitory concentration (MIC) and growth curves against VRE were also evaluated. The liberation of cellular contents, as well as changes in cell membrane permeability, have been studied. The MIC value of the essential oil against Vancomycin-resistant Enterococci was 15.625 μg/mL speculating that the essential oil seemed to be effective against the drug-resistant culture. When the essential oil of Cinnamomum cassia was administered to the bacterial culture, the constituents of the bacterial cell were expelled into the medium.

Characterization of a genomic Island carrying the tet(X4) gene in porcine Acinetobacter towneri co-harboring plasmid-borne bla NDM-1 and bla OXA-58 genes.

Tigecycline and carbapenems are last-resort antimicrobial agents to treat serious infections caused by multi-drug resistant bacterial pathogens. However, the co-occurrence of tigecycline and carbapenem resistance determinants challenges the clinical efficacy of these antimicrobial agents. In this study, we report the co-existence of tet(X4), blaNDM−1 and blaOXA−58 genes in the porcine Acinetobacter towneri isolate 19110F47. Sequence analysis revealed that tet(X4) gene, along with the florfenicol resistance gene floR, was flanked by three copies of IS91-like elements, which can form three different translocatable units (TUs), and were located in a 41,098-bp multidrug resistance region (MDRR) within a novel 100,354-bp genomic island (GI) region. TUs comprising floR-virD2-ISVsa3, hp-abh-tet(X4)-ISVsa3 and virD2-floR-ISVsa3-hp-abh-tet(X4)-ISVsa3 can be looped out from the chromosomal DNA and facilitate the transfer of the TU-based resistance genes into other plasmidic or chromosomal sites. In addition, the carbapenemase genes blaNDM−1 and blaOXA−58 were found on different non-conjugative multiresistance plasmids in this isolate, with the genetic contexts ISAba125-blaNDM−1-bleMBL-tnpR and ΔISAba3-blaOXA−58-ISAba3, respectively. The simultaneous occurrence of tet(X4), blaNDM−1 and blaOXA−58 in the same porcine A. towneri isolate emphasizes the importance of antimicrobial resistance surveillance in food-producing animals.

In Silico Study for Algerian Essential Oils as Antimicrobial Agents against Multidrug-Resistant Bacteria Isolated from Pus Samples.

In the context of the globally growing problem of resistance to most used antibacterial agents, essential oils offer promising solutions against multidrug-resistant (MDR) bacterial pathogens. The present study aimed to evaluate the prevalence, etiology, and antibiotic-resistance profiles of bacteria responsible for pyogenic infections in Regional Military University Hospital of Constantine. Disc diffusion and broth microdilution (MIC) methods were used to evaluate the antimicrobial activity of essential oils from five Algerian aromatic plants growing wild in the north of Algeria—Salvia officinalis (Sage), Thymus vulgaris (Thyme), Mentha pulegium L. (Mentha), Rosmarinus officinalis (Rosemary), and Pelargonium roseum (Geranium)—against reference and MDR strains. During three months of the prospective study, 112 isolates out of 431 pus samples were identified. Staphylococcus aureus was the most predominant species (25%), followed by Klebsiella pneumoniae (21.42%), Pseudomonas aeruginosa (21%), and Escherichia coli (17.95%). Among pus isolates, 65 were MDR (58.03%). The radial streak-line assay showed that R. officinalis and M. pulegium L. had weak activity against the tested strains, whereas P. roseum showed no activity at all. Meanwhile, T. vulgaris was the most potent, with an inhibition zone of 12–26 mm and an MIC value ranging between 0.25 and 1.25%, followed by S. officinalis with an inhibition zone of 8–12 mm and an MIC value ranging between 0.62 and 2.5%. Generally, A. baumannii and S. aureus ATCC6538P were the most sensitive strains, whereas P. aeruginosa ATCC27853 was the most resistant strain to the oils. Gas chromatography–mass spectrometry analysis of chemical composition revealed the presence of borneol (76.42%) and thymol (17.69%) as predominant in thyme, whereas camphor (36.92%) and α- thujone (34.91%) were the major volatiles in sage. The in-silico study revealed that sesquiterpenes and thymol had the highest binding free energies against the vital enzymes involved in biosynthesis and repair of cell walls, proteins, and nucleic acids compared to monoterpenes. The results demonstrated that T. vulgaris and S. officinalis are ideal candidates for developing future potentially active remedies against MDR strains.

Antibacterial effects of vanilla ingredients provide novel treatment options for infections with multidrug-resistant bacteria - A recent literature review.

Due to the increasing application of antibiotics not only in healthcare settings but also in conventional agriculture and farming, multidrug-resistant (MDR) bacterial pathogens are rising worldwide. Given the increasing prevalence of infections caused by MDR bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (ESKAPE pathogen complex), it is pivotal to explore novel alternative or adjunct treatment options such as phytochemicals with antibiotic properties. Vanillin and vanillin acid represent biologically active ingredients in vanilla that has been known for long for its health-beneficial including antimicrobial effects besides its role as flavoring agent. Therefore, we performed a literature search from the past 10 years summarizing the knowledge regarding the effects of vanilla constituents against bacterial including MDR pathogens. Our survey revealed that vanillin and vanillic acid exerted potent effects directed against distinct Gram-positive and Gram-negative bacteria by inhibiting growth, viability, biofilm formation, quorum sensing and virulence. Remarkably, when combining vanillin or vanillic acid with defined synthetic antibiotics pronounced synergistic effects directed against distinct pathogenic including ESCAPE strains could be observed. In conclusion, vanilla ingredients constitute promising alternative or adjunct options in the combat of infections caused by MDR bacterial pathogens.

Novel and Structurally Diversified Bacterial DNA Gyrase Inhibitors Discovered through a Fluorescence-Based High-Throughput Screening Assay.

Bacterial DNA gyrase, a type IIA DNA topoisomerase that plays an essential role in bacterial DNA replication and transcription, is a clinically validated target for discovering and developing new antibiotics. In this article, based on a supercoiling-dependent fluorescence quenching (SDFQ) method, we developed a high-throughput screening (HTS) assay to identify inhibitors targeting bacterial DNA gyrase and screened the National Institutes of Health's Molecular Libraries Small Molecule Repository library containing 370,620 compounds in which 2891 potential gyrase inhibitors have been identified. According to these screening results, we acquired 235 compounds to analyze their inhibition activities against bacterial DNA gyrase using gel- and SDFQ-based DNA gyrase inhibition assays and discovered 155 new bacterial DNA gyrase inhibitors with a wide structural diversity. Several of them have potent antibacterial activities. These newly discovered gyrase inhibitors include several DNA gyrase poisons that stabilize the gyrase-DNA cleavage complexes and provide new chemical scaffolds for the design and synthesis of bacterial DNA gyrase inhibitors that may be used to combat multidrug-resistant bacterial pathogens. Additionally, this HTS assay can be applied to screen inhibitors against other DNA topoisomerases.

Facile construction of fluorescent C70-COOH nanoparticles with advanced antibacterial and anti-biofilm photodynamic activity.

Photodynamic antibacterial therapy has been considered as one of the most promising treatments to alleviate the spread of multidrug resistant bacterial pathogens. Given the hypoxic environment of infectious tissues, photosensitizers with reduced oxygen-demand could exhibit superiority upon irradiation. Herein reported is a novel C70-based photosensitizers synthesized by the facile one-step thiol-ene reaction. Various characterization techniques were employed to confirm the structural, photoluminescent properties, photostability and biocompatibility of the as-synthesized C70-COOH nanoparticles. Furthermore, they were capable of efficiently producing reactive oxygen species following both the type I and II mechanistic pathways, thus still generating adequate free radicals under hypoxic condition. Therefore, they could approach and destroy the bacterial cell membrane in the presence of visible light, thereby causing cytoplasmic leakage and eventually achieving broad-spectrum inactivation of four representative bacterial strains. Especially, methicillin-resistant Staphylococcus aureus (MRSA) were completely eliminated after merely 10 minutes irradiation, and the formation of its corresponding biofilm were also greatly inhibited by C70-COOH nanoparticles. These results provide new insights and opportunities for the development of hypoxia-tolerant fullerene-based photosensitizers to combat multidrug resistant bacterial and related infections.

Bacterial Isolates and Antibacterial Resistance Patterns in a Patient with Acute Exacerbation of Chronic Obstructive Pulmonary Disease in a Tertiary Teaching Hospital, Southwest Ethiopia.

Introduction Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. The natural course of COPD is characterized by acute exacerbation. Infectious agents, particularly bacteria, cause exacerbation of COPD in the majority. This study aimed to determine the bacteriology and antibiotic resistance patterns among patients with acute exacerbations of COPD (AECOPD) at Jimma Medical Center. Methods A cross-sectional study was conducted from March to October 2019. Demographic, clinical, and sputa samples were collected from 39 study participants, who were diagnosed with AECOPD. Bacterial pathogens were identified using standard bacteriological techniques, and anti-microbial susceptibility testing was done by Kirby Bauer's disk diffusion method. Extended-spectrum β-lactamase (ESβL) and carbapenemase production were confirmed by MASTTM D68C and MASTTM D73C combination disc sets, respectively. Chi-square and odds ratios were calculated. Results Overall, 69.2% (27/39) of sputum samples were confirmed to be culture-positive. A total of 32 bacterial isolates with 78.1% (25/32) Gram-negative and 21.9% (7/32) Gram-positive bacteria were identified. The predominant bacterial isolates were Pseudomonas aeruginosa 21.9% (7/32), Klebsiella pneumoniae 18.75% (6/32), and Staphylococcus aureus 15.62% (7/32). Overall, 30 (93.8%) of the isolates were multidrug-resistant (MDR). About 48% (12/25) and 8 (32%)of gram negative bacterial isolates were ESBL betalatemase and OXA-48 carbapenemase producers, respectively. Having two or more exacerbation experiences in the previous year were found to be important determinants of the sputum culture positivity. Conclusions High rates of MDR, ESBL, and carbapenemase producer bacteria were isolated from patients with AECOPD. Empiric antibiotic therapy should consider the prevalence of antibiotic-resistant pathogens and the factor that may increase the occurrence of MDR bacterial pathogens.

Absinthe against multi-drug resistant bacterial pathogens? A recent update on the antibacterial effects of Artemisia compounds.

The widespread misuse of antibiotics leads to a rapid development of multi-drug resistant (MDR) bacterial pathogens all over the globe, resulting in serious difficulties when treating infectious diseases. Possible solutions are not limited to the development of novel synthetic antibiotics but extend to application of plant-derived products either alone or in combination with common antibiotics. The aim of this actual review was to survey the literature from the past 10 years regarding the antibacterial effects of distinct Artemisia species including Artemisia absinthiae constituting an integral component of the Absinthe drink. We further explored the synergistic antibacterial effects of the Artemisia plant products with established antibiotics. The survey portrays the Artemisia derived compounds as potent antibacterial agents that can even restore the efficacy of antibiotics against MDR bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and MDR Escherichia coli. This, in turn, is presumably triggered in part by the interaction of the Artemisia ingredients with the efflux pumps of MDR bacteria. In conclusion, biologically active molecules in Artemisia plants enhance the antibiotic susceptibility of resistant bacteria, which provide promising future therapeutic strategies to combat MDR bacterial pathogens.

Impact of the WHO Integrated Stewardship Policy on the Control of Methicillin-Resistant Staphyloccus aureus and Third-Generation Cephalosporin-Resistant Escherichia coli: Using a Mathematical Modeling Approach.

Methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (3GCREc) are community and hospital-associated pathogens causing serious infections among populations by infiltrating into hospitals and surrounding environment. These main multi-drug resistant or antimicrobial resistance (AMR) bacterial pathogens are threats to human health if not properly tackled and controlled. Tackling antimicrobial resistance (AMR) is one of the issues for the World Health Organization (WHO) to design a comprehensive set of interventions which also helps to achieve the end results of the developing indicators proposed by the same organization. A deterministic mathematical model is developed and studied to investigate the impact of the WHO policy on integrated antimicrobial stewardship activities to use effective protection measures to control the spread of AMR diseases such as MRSA and 3GCREc in hospital settings by incorporating the contribution of the healthcare workers in a hospital and the environment in the transmission dynamics of the diseases. The model also takes into account the parameters describing various intervention measures and is used to quantify their contribution in containing the diseases. The impact of combinations of various possible control measures on the overall dynamics of the disease under study is investigated. The model analysis suggests that the contribution of the interventions: screening and isolating the newly admitted patients, improving the hygiene in hospital settings, decolonizing the pathogen carriers, and increasing the frequency of disinfecting the hospital environment are effective tools to contain the disease from invading the population. The study revealed that without any intervention, the diseases will continue to be a major cause of morbidity and mortality in the affected communities. In addition, the study indicates that a coordinated implementation of the integrated control measures suggested by WHO is more effective in curtailing the spread of the diseases than piecemeal strategies. Numerical experiments are provided to support the theoretical analysis.

Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens.

The rapid emergence and spread of multidrug-resistant (MDR) bacterial pathogens pose a serious danger to worldwide human health, and resistance to last-resort drugs, such as polymyxins, is being increasingly detected in MDR Gram-negative pathogens. There is an urgent need to find and optimize combination therapies as an alternative therapeutic strategy, with a dry pipeline in novel antibiotic research and development. We found a monoester formed from the combination of lauric acid and glycerol, glycerol monolaurate (GML), possessing prominent antibacterial and anti-inflammatory activity. However, it is still unclear whether GML in combination could increase antimicrobial activity. Here, we reported that polymyxin B (PMNB) combined with GML exhibited a synergistic antimicrobial impact on Gram-negative strains in vitro, including clinical MDR isolates. This synergistic antimicrobial activity correlated with the destruction of bacterial cell structures, eradication of preformed biofilms, and increased reactive oxygen species (ROS) accumulation. We also showed that PMNB synergized with GML effectively eliminated pathogens from bacterial pneumonia caused by Klebsiella pneumoniae to rescue mice. Our research demonstrated that the PMNB and GML combination induced synergistic antimicrobial activity for Gram-negative pathogens in vitro and in vivo. These findings are of great importance for treating bacterial infections and managing the spread of infectious diseases.