Resistant Gram-positive Bacteria Research Articles

Metabolic and Lipidomic Assessment of Kidney Cells Exposed to Nephrotoxic Vancomycin Dosages.

Vancomycin is a glycopeptide antibiotic used against multi-drug resistant gram-positive bacteria such as Staphylococcus aureus (MRSA). Although invaluable against resistant bacteria, vancomycin harbors adverse drug reactions including cytopenia, ototoxicity, as well as nephrotoxicity. Since nephrotoxicity is a rarely occurring side effect, its mechanism is incompletely understood. Only recently, the actual clinically relevant concentration the in kidneys of patients receiving vancomycin was investigated and were found to exceed plasma concentrations by far. We applied these clinically relevant vancomycin concentrations to murine and canine renal epithelial cell lines and assessed metabolic and lipidomic alterations by untargeted and targeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses. Despite marked differences in the lipidome, both cell lines increased anabolic glucose reactions, resulting in higher sorbitol and lactate levels. To the best of our knowledge, this is the first endometabolic profiling of kidney cells exposed to clinically relevant vancomycin concentrations. The presented study will provide a valuable dataset to nephrotoxicity researchers and might add to unveiling the nephrotoxic mechanism of vancomycin.

Vancomycin-Induced Neutropenia with Fever

Vancomycin is a glycopeptide antibiotics acts by inhibiting cell well and is used for the treatment of resistant Gram-positive bacteria. Vancomycin-induced fever with neutropenia is not commonly encountered in our clinical practice, it can lead to diagnostic dilemmas during the course of management. We report the case of a 43-year-old female with infective endocarditis of the aortic valve, who was started empirically on vancomycin and ceftriaxone. She later developed fever with neutropenia following 2 weeks of intravenous antibiotics. This was attributed to the rare adverse effect of vancomycin, after further investigating and ruling out all other possible etiologies. After discontinuing vancomycin, the symptoms resolved rapidly. Although the exact mechanism of the fever and neutropenia is not known, many researchers believe it to be immune mediated.

Is Hinokitiol Efficacious Against an Antimicrobial-Resistant Strain of Streptococcus pyogenes? A Research Protocol

Introduction: Streptococcus pyogenes, a highly infectious and deadly gram-positive bacterium in the Group A Streptococcus family, that causes respiratory and skin infections. Treatments include oral penicillin and macrolides; however, penicillin and macrolide-resistant Streptococcus pyogenes (e.g., A458) are emerging. Hinokitiol, beta-thujaplicin, has been thought to be an alternative solution to help fight against antimicrobial resistant strains of S. pyogenes as several studies have highlighted its bactericidal effects. These effects in turn, inhibit the production of bacterial adenosine triphosphate and bacteriostatic effects (growth inhibition) of hinokitiol on a related bacterium, Streptococcus pneumoniae and a variant of Streptococcus pyogenes, SSI-9. Furthermore, hinokitiol was found to be very efficacious against a penicillin and macrolide resistant gram-positive bacterium, indicating that penicillin and macrolides likely have a different mechanism of action from hinokitiol. This suggests that microbes are likely not resistant to hinokitiol. Therefore, by extrapolating this data, it is thought that hinokitiol may be efficacious in combatting A458, a concerning antimicrobial resistant strain of Streptococcus pyogenes. Methods: Every step would be performed under triple-blind conditions. Using a solvent control, penicillin G, streptomycin, and hinokitiol, an efficacy trial would be undertaken to evaluate the bactericidal/inhibitory effects of each drug and determine whether hinokitiol is superior to the current gold-standards. A two-way analysis of variance and multiple repeated-measures analysis of variance will be used to evaluate efficacy. Results: It is expected that hinokitiol is efficacious against the resistant strain of Streptococcus pyogenes, A458 unlike streptomycin. Discussion: The strengths of this study are that a novel treatment was used and the experiment was conducted as a triple-blinded experiment. The limitations include its efficiency and the lack of knowledge of the treatment. The statistical test conducted for this study would evaluate whether hinokitiol has a statistically significant effect on a resistant strain of Streptococcus pyogenes. Conclusion: It is likely that hinokitiol will show a resistance-free effect on the two strains of Streptococcus pyogenes. This is a significant undertaking due to the dangers of antimicrobial-resistant Streptococcus pyogenes. However, further experiments need to be conducted to support this hypothesis.

Synthesis, In Silico and In Vitro Antimicrobial Evaluation of Cyanoketene S,N-Acetals and Their Pyrazoles Against Staphylococcus Aureus DNA Gyrase Enzyme

Objectives: The continuous reporting of bacterial resistance to antibiotics is an ongoing challenge that can be life-threatening. Actions to develop new chemicals to overcome the bacterial resistance has gained a significant importance. Methods: A series of ketene S,N-acetals 4a-k and their pyrazoles 6a-k were synthesized and their structures were established by spectral data. Membrane permeability predictions and in vitro antimicrobial activity against multi-drug resistant (MDR) Gram-positive bacteria and other microorganisms was determined. The binding affinity with DNA gyrase was assessed using in silico studies in comparison to ciprofloxacin then tthe gyrase inhibition assay was conducted to detect the mode of action. Results: All the synthesized compounds have a good affinity to pass through the phospholipid membrane of Staphylococcus aureus (S. aureus). Compound 6g exhibited the most potent antibacterial activity with MIC values ranged between 16 and 32 µg/mL. The compound also showed a higher binding affinity than ciprofloxacin with DNA gyrase in the in silico studies and this effect was clearly shown by a very good IC50 value of the gyrase inhibition assay. Conclusions: According to our data, compound 6g is a possible candidate to act against MDR bacteria and its main mode of action is through inhibition of the gyrase enzyme, further modifications are still required to enhance its activity.

Prevalence, Sensitivity Profile and Resistance of Gram-Positive Bacteria in Wounds to Conventional Antibiotics

Aim: The prevalence, sensitivity profile and resistance of Gram-positive bacteria in wounds to commercial antibiotics were ascertained in this study.
 Place and duration of study: University of Medical Sciences Teaching Hospital, Akure, Nigeria, between January and June 2019.
 Methodology: Wound swabs sample collection, isolation of bacteria, identification of Gram-positive bacteria isolates and antibiotics sensitivity testing of isolated bacteria were determined employing standard protocols.
 Result: Three Gram-positive bacteria were isolated and presumptively identified to be S. aureus, S. epidermidis and S. pyogenes. S. aureus had the highest prevalence of 53% followed by S. epidermidis with 42% and S. pyogenes accounting for the least occurrence of 5%. Ninety percent (90%) of ten S. aureus strains were resistant to ciprofloxacin while only 10% had intermediate activity. The least resistance of S. aureus strains was against pefloxacin (40%), while to streptomycin, 87.5% of eight S. epidermidis strains were resistant and 12.5% had intermediate sensitivity. Susceptibility was observed in S. epidermidis against pefloxacin (12.5%) while 50% had intermediate sensitivity and 37.5% were resistant. The highest zone of inhibition of S. epidermidis was observed in strain 7 against pefloxacin (16.00±1.00 mm) and in S. aureus by strain 5 against pefloxacin (16.50±2.50 mm).
 Conclusion: Pefloxacin-sensitive Staphylococcus and Streptococcus species from wound swabs could become resistant overtime and this calls for incessant vigilance on Gram-positive wound bacteria antibiotic-susceptibility appraisal particularly in an antibiotics-abuse setting.

Efficacy and Safety of Intraventricular Antibiotic Administration

Abstract The administration of antibiotics via intraventricular administration for treatment of central nervous system infections is an understudied topic that lacks data for specific patient outcomes regarding dosing and adverse events. A comprehensive review of the literature was performed on PubMed, MEDLINE, Scopus, and CINAHL using the following terminology: “intraventricular” OR “intraventricular drug administration” AND “antibiotic” OR “antimicrobial” AND “infection” AND “CNS” NOT “Intrathecal.” Studies that described adult human patients who received an antibiotic via intraventricular administration with complete dosing, efficacy, and safety data were included. A total of 8 studies met inclusion and were used in this review and detailed the use of antibiotics targeting resistant Gram-positive and Gram-negative bacteria. Minimal adverse effects were reported, although the determination of appropriate dosing and markers of efficacy remains elusive due to the common concomitant administration of intravenous antibiotics. Further clinical evaluation is necessary.

Rhodomyrtone Accumulates in Bacterial Cell Wall and Cell Membrane and Inhibits the Synthesis of Multiple Cellular Macromolecules in Epidemic Methicillin-Resistant Staphylococcusaureus.

As the burden of antibacterial resistance worsens and treatment options become narrower, rhodomyrtone—a novel natural antibiotic agent with a new antibacterial mechanism—could replace existing antibiotics for the treatment of infections caused by multi-drug resistant Gram-positive bacteria. In this study, rhodomyrtone was detected within the cell by means of an easy an inexpensive method. The antibacterial effects of rhodomyrtone were investigated on epidemic methicillin-resistant Staphylococcus aureus. Thin-layer chromatography demonstrated the entrapment and accumulation of rhodomyrtone within the bacterial cell wall and cell membrane. The incorporation of radiolabelled precursors revealed that rhodomyrtone inhibited the synthesis of macromolecules including DNA, RNA, proteins, the cell wall, and lipids. Following the treatment with rhodomyrtone at MIC (0.5–1 µg/mL), the synthesis of all macromolecules was significantly inhibited (p ≤ 0.05) after 4 h. Inhibition of macromolecule synthesis was demonstrated after 30 min at a higher concentration of rhodomyrtone (4× MIC), comparable to standard inhibitor compounds. In contrast, rhodomyrtone did not affect lipase activity in staphylococci—both epidemic methicillin-resistant S. aureus and S. aureus ATCC 29213. Interfering with the synthesis of multiple macromolecules is thought to be one of the antibacterial mechanisms of rhodomyrtone.

Design, synthesis, and antibacterial evaluation of PFK-158 derivatives as potent agents against drug-resistant bacteria

Infections caused by antibiotic resistant bacteria are a major health concern throughout the world. It is well known that PFK-158 can enhance the antibacterial effect of polymyxin, but its own anti-bactericidal effect is rarely discussed. In order to investigate the anti-bactericidal effect of PFK-158 and its derivatives, PFK-158 and 35 derivatives were designed, synthesized, and evaluated for their antibacterial activities. Compounds A1, A3, A14, A15 and B6 exhibited potent antibacterial effect against both clinical drug sensitive and resistant Gram-positive bacteria, and they are 2–8 folds more potent than levofloxacin against Methicillin-resistant staphylococcus epidermidis (MRSE). A significant synergistic effect of these compounds and polymyxin against drug-resistant Gram-negative bacteria, which is similar to PFK-158 was also observed. The result can provided a new and broader prospect for the development of new medicine against drug-resistant bacteria.

English

Globally, there is an increasing report of bacterial resistance to currently available antibiotics. The urgent need for newer therapeutic modalities was the incentive for the current evaluation of bactericidal and inhibitory effects of methanolic and aqueous extracts of Mitracarpus villosus on selected antibiotic resistant Gram-positive and Gram-negative bacteria. Ten-fold serial dilution was used to test the effects of the extracts. The percentage yield of extractable components was 22% for methanol and 8.3% for water. The minimum inhibitory concentration (MIC) of methanolic extract was 0.001 mg/mL against Streptococcus pyogenes, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Salmonella Typhi showing resistance to antibiotics and 0.01 mg/mL for Staphylococcus aureus, Bacillus subtilis, and Klebsiella pneumoniae while the minimum bactericidal concentration (MBC) was 0.1 mg/mL for all the isolates except S. aureus and E. coli with MBC of 0.01 mg/mL. Similarly, the MIC of aqueous extract was 0.01 mg/mL for S. pyogenes, S. aureus, B. subtilis, and K. pneumoniae; 0.1 mg/mL against S. faecalis and E. coli; 0.001 mg/mL against P. aeruginosa and S. typhi. The MBC of the aqueous extract at 0.1 mg/mL was active against S. pyogenes, S. faecalis, P. aeruginosa, K. pneumonia, and S. typhi; 1.0 mg/mL was active against S. aureus, B. subtilis, and E. coli. Findings from the present study indicate that the extracts of M.  villosus have the potential to be used for treatment and cure of infections caused by selected bacteria. The methanolic extracts show more potent activity. Further study on a larger scale at varied concentrations including a test for potential toxicity in cultured cells are needed to depict their safety profiles before recommendation for inclusion in the antibacterial armamentarium.   Key words: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), M. villosus, bioactive compounds.

Targeted Conservative Cointegrate Formation Mediated by IS26 Family Members Requires Sequence Identity at the Reacting End.

IS26 forms cointegrates using two distinct routes, a copy-in mechanism involving one insertion sequence (IS) and a target and a targeted conservative mechanism involving two ISs in different DNA molecules. In this study, the ability of IS26 and some close relatives, IS1006, IS1008, and a natural hybrid, IS1006/IS1008, which are found predominantly in Acinetobacter spp., to interact was examined. IS1006/1008 consists of 175 bp from IS1006 at the left end, with the remainder from IS1008. These ISs all have the same 14-bp terminal inverted repeats, and the Tnp26, Tnp1006, and Tnp1008 transposases, with pairwise identities of 83.7% to 93.1%, should be able to recognize each other's ends. In a recA-negative Escherichia coli strain, IS1006, IS1008, and IS1006/1008 each formed cointegrates via the copy-in route and via the targeted conservative route, albeit at frequencies for the targeted reaction at least 10-fold lower than for IS26 However, using mixed pairs, targeted cointegration was detected only when IS1008 was paired with the IS1006/1008 hybrid, which also encodes Tnp1008, and the targeted cointegrates formed all arose from a reaction occurring at the end where the DNA sequences are identical. The reaction also occurred at the end with extended DNA identity using IS26 paired with IS26::catA1, an artificially constructed IS26 derivative that includes the catA1 gene. Thus, both identical transposases and identical DNA sequences at the reacting end were required. These features indicate that the targeted conservative pathway proceeds via a single transposase-catalyzed strand transfer, followed by migration and resolution of the Holliday junction formed.IMPORTANCE The IS26 family includes the ISs that are commonly found associated with antibiotic resistance genes in multiply resistant Gram-negative and Gram-positive bacteria. IS26 is most prevalent in Gram-negative species and can generate the clusters of antibiotic resistance genes interspersed with directly oriented IS26 seen in multiply resistant pathogens. This ability relies on the novel dual mechanistic capabilities of IS26 family members. However, the mechanism underlying the recently discovered targeted conservative mode of cointegrate formation mediated by IS26, IS257/IS431, and IS1216, which is unlike any previously studied IS movement mechanism, is not well understood. An important question is what features of the IS and the transposase are key to allowing IS26 family members to undertake targeted conservative reaction. In this study, this question was addressed using mixed-partner crosses involving IS26 and naturally occurring close relatives of IS26 that are found near resistance genes in Acinetobacter baumannii and are widespread in Acinetobacter species.

Bacterial Cell Wall Analogue Peptides Control the Oligomeric States and Activity of the Glycopeptide Antibiotic Eremomycin: Solution NMR and Antimicrobial Studies.

For some time, glycopeptide antibiotics have been considered the last line of defense against Methicillin-resistant Staphylococcus aureus (MRSA). However, vancomycin resistance of Gram-positive bacteria is an increasingly emerging worldwide health problem. The mode of action of glycopeptide antibiotics is essentially the binding of peptidoglycan cell-wall fragments terminating in the d-Ala-d-Ala sequence to the carboxylate anion binding pocket of the antibiotic. Dimerization of these antibiotics in aqueous solution was shown to persist and even to enhance the antibacterial effect in a co-operative manner. Some works based on solid state (ss) Nuclear Magnetic Resonance (NMR) studies questioned the presence of dimers under the conditions of ssNMR while in a few cases, higher-order oligomers associated with contiguous back-to-back and face-to-face dimers were observed in the crystal phase. However, it is not proved if such oligomers persist in aqueous solutions. With the aid of 15N-labelled eremomycin using 15N relaxation and diffusion NMR methods, we observed tetramers and octamers when the N-Ac-d-Ala-d-Ala dipeptide was added. To the contrary, the N-Ac-d-Ala or (N-Ac)2-l-Lys-d-Ala-d-Ala tripeptide did not induce higher-order oligomers. These observations are interesting examples of tailored supramolecular self-organization. New antimicrobial tests have also been carried out with these self-assemblies against MRSA and VRE (resistant) strains.

Assessment of in vitro and in vivo Antimicrobial Activity of an Isonitrosomalononitrile Silver(I) Salt

The design and evaluation of antimicrobial activities of an isonitrosomalononitrile silver(I) salt was reported. This highly stable water-soluble silver salt shows Minimum Inhibitory Concentrations (MIC) values ranging from 0.15 to 5 µg/mL towards both sensitive and resistant Gram-positive and negative bacteria. Furthermore, this silver salt has been investigated for its ability to treat a S. aureus infected Galleria mellonella larvae animal model with promising results. Thus, our results demonstrated that 80% of the treated larvae survived after 24h with respect to 10% of the untreated ones, respectively.

In Vitro activity of a Novel Benzoquinolizine Antibiotic, Levonadifloxacin (WCK 771) against Blood Stream Gram-Positive Isolates from a Tertiary Care Hospital.

Background Blood stream infections (BSIs) due to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality ranging from 10 to 60%. The current anti-MRSA agents have limitations with regards to safety and tolerability profile which limits their prolonged usage. Levonadifloxacin and its oral prodrug alalevonadifloxacin, a novel benzoquinolizine antibiotic, have recently been approved for acute bacterial skin and skin structure infections including diabetic foot infections and concurrent bacteremia in India. Methods The present study assessed the potency of levonadifloxacin, a novel benzoquinolizine antibiotic, against Gram-positive blood stream clinical isolates ( n = 31) collected from January to June 2019 at a tertiary care hospital in Mumbai, India. The susceptibility of isolates to antibacterial agents was defined following the Clinical and Laboratory Standard Institute interpretive criteria (M100 E29). Results High prevalence of MRSA (62.5%), quinolone-resistant Staphylococcus aureus (QRSA) (87.5%), and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) (82.35%) were observed among bacteremic isolates. Levonadifloxacin demonstrated potent activity against MRSA, QRSA, and MR-CoNS strains with significantly lower minimum inhibitory concentration MIC 50/90 values of 0.5/1 mg/L as compared with levofloxacin (8/32 mg/L) and moxifloxacin (2/8 mg/L). Conclusion Potent bactericidal activity coupled with low MICs support usage of levonadifloxacin for the management of BSIs caused by multidrug resistant Gram-positive bacteria.

Development of a 51-hospital Chicagoland regional antibiogram and comparison to local hospital and national surveillance data.

To develop a regional antibiogram within the Chicagoland metropolitan area and to compare regional susceptibilities against individual hospitals within the area and national surveillance data. Multicenter retrospective analysis of antimicrobial susceptibility data from 2017 and comparison to local institutions and national surveillance data. The analysis included 51 hospitals from the Chicago-Naperville-Elgin Metropolitan Statistical Area within the state of Illinois. Overall, 18 individual collaborator hospitals provided antibiograms for analysis, and data from 33 hospitals were provided in aggregate by the Becton Dickinson Insights Research Database. All available antibiogram data from calendar year 2017 were combined to generate the regional antibiogram. The final Chicagoland antibiogram was then compared internally to collaborators and externally to national surveillance data to assess its applicability and utility. In total, 167,394 gram-positive, gram-negative, fungal, and mycobacterial isolates were collated to create a composite regional antibiogram. The regional data represented the local institutions well, with 96% of the collaborating institutions falling within ±2 standard deviations of the regional mean. The regional antibiogram was able to include 4-5-fold more gram-positive and -negative species with ≥30 isolates than the median reported by local institutions. Against national surveillance data, 18.6% of assessed pathogen-antibiotic combinations crossed prespecified clinical thresholds for disparity in susceptibility rates, with notable trends for resistant gram-positive and gram-negative bacteria. Developing an accurate, reliable regional antibiogram is feasible, even in one of the largest metropolitan areas in the United States. The biogram is useful in assessing susceptibilities to less commonly encountered organisms and providing clinicians a more accurate representation of local antimicrobial resistance rates compared to national surveillance databases.

Eco-friendly synthesis of silver nanoparticles from the whole plant of Cleome viscosa and evaluation of their characterization, antibacterial, antioxidant and antidiabetic properties.

The current research is to develop an easy and eco-friendly method for the synthesis of three different concentrations of silver nanoparticles (1mMCvAgNPs, 2mMCvAgNPs and 3mMCvAgNPs) using aqueous whole plant extract of Cleome viscosa and to evaluate their antibacterial, antioxidant and antidiabetic properties. CvAgNPs were characterized by Using UV-vis spectrophotometer, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM) and transmission electron microscope (TEM). The formation of CvAgNPs was confirmed by the observation of band between 250nm to 600nm UV-vis spectrum. The crystalline structure of CvAgNPs with a face-centered cubic (FCC) was confirmed by XRD. The responsible phytochemicals for the reduction and capping material of CvAgNPs were observed with FT-IR. The SEM analysis confirmed the size and shapes of CvAgNPs. The CvAgNPs have shown the rich content of total phenolic and total flavonoid components. The CvAgNPs have shown significant antibacterial activity on multi drug resistance Gram-negative and Gram-positive bacteria and also have shown significant strong antioxidant activities (DPPH, ABTS, H2O2 scavenging, Phosphomolybdenum assay and reducing power). The inhibitory action of CvAgNPs on α-glucosidase and α-amylase was stronger than the inhibitory action of acarbose. To best of our knowledge, this is the first attempt on the synthesis of AgNPs using C. viscosa whole plant aqueous extract. The synthesized CvAgNPs exhibited good antimicrobial, antioxidant and antidiabetic properties. Hence, to validate our results, the in vivo studies at the molecular level are needed to develop Cleome viscosa as an antibacterial, antioxidant and anti-diabetic agent.

Actividad antimicrobiana de metabolitos secundarios de Aspergillus fumigatus sensu stricto sobre cepas clínicas de Staphylococcus aureus y Streptococcus pneumoniae

Introducción. La resistencia a los antibióticos de bacterias Gram positivas es un grave problema de salud pública donde algunas medidas paliativas pueden encontrarse en los principios antimicrobianos de hongos filamentosos. Objetivo. Evaluar la actividad antimicrobiana de metabolitos secundarios de un aislamiento clínico de Aspergillus fumigatus sobre cepas clínicas de Staphylococcus aureus y Streptococcus pneumoniae. Métodos. La fermentación líquida de A. fumigatus se realizó en un caldo líquido sulfato, papa y dextrosa, utilizando acetato de etilo para la extracción de metabolitos. Mediante la metodología de disco difusión se evaluó la actividad antimicrobiana considerada como un halo mayor de 6 mm. Resultados. Se obtuvo una media de 24,02 ± 2,51 mm y 23,62 ± 4,68 mm de halo de inhibición sobre Staphylococcus aureus sensible y resistente oxacilina, respectivamente. Para Streptococcus pneumoniae sensibles y no sensibles a penicilina las medias fueron de 25,82 ± 4,05 mm y 26,5 ± 5,39 mm, respectivamente. Conclusiones. El extracto crudo de A. fumigatus posee metabolitos secundarios de naturaleza alcaloide y esteroles insaturados con actividad antimicrobiana.

Antimicrobial Capacity of Plant Polyphenols against Gram-positive Bacteria: A Comprehensive Review.

Multi-drug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) disseminate rapidly amongst patients in healthcare facilities and suppose an increasingly important cause of community-associated infections and associated mortality. The development of effective therapeutic options against resistant bacteria is a public health priority. Plant polyphenols are structurally diverse compounds that have been used for centuries for medicinal purposes, including infections treatment and possess, not only antimicrobial activity, but also antioxidant, anti-inflammatory and anticancer activities among others. Based on the existing evidence on the polyphenols' antibacterial capacity, polyphenols may be postulated as an alternative or complementary therapy for infectious diseases. To review the antimicrobial activity of plant polyphenols against Gram-positive bacteria, especially against S. aureus and its resistant strains. Determine the main bacterial molecular targets of polyphenols and their potential mechanism of action. The most relevant reports on plant polyphenols' antibacterial activity and their putative molecular targets were studied. We also performed virtual screening of thousand different polyphenols against proteins involved in the peptidoglycan biosynthesis to find potential valuable bioactive compounds. The bibliographic information used in this review was obtained from MEDLINE via PubMed. Several polyphenols: phenolic acids, flavonoids (especially flavonols), tannins, lignans, stilbenes and combinations of these in botanical mixtures, have exhibited significant antibacterial activity against resistant and non-resistant Gram-positive bacteria at low μg/mL range MIC values. Their mechanism of action is quite diverse, targeting cell wall, lipid membrane, membrane receptors and ion channels, bacteria metabolites and biofilm formation. Synergic effects were also demonstrated for some combinations of polyphenols and antibiotics. Plant polyphenols mean a promising source of antibacterial agents, either alone or in combination with existing antibiotics, for the development of new antibiotic therapies.

Evaluation of the Effect of Contezolid (MRX-I) on the Corrected QT Interval in a Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study in Healthy Chinese Volunteers

Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1,600 mg) dose, placebo, and oral moxifloxacin at 400 mg in four separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (ΔΔQTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for ΔΔQTc was slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 h postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin, at 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 by having a lower confidence bound of ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and ΔQTcF interval with a slope of 0.227 ms per mg/liter (90% CI, 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

Potential uses of Lipopolysaccharide and Exopolysaccharide Isolated from Agrobacterium spp.

A gram-negative bacterium, Agrobacterium, synthesizes lipopolysaccharide and exopolysaccharide, both indispensable in establishing complex interactions with plant hosts. These polysaccharides have biocontrol applications. This study intended to determine: 1) LPS potential as insecticide; 2) EPS production capacity. LPSs obtained from Agrobacterium isolates were tested for insecticidal activity against test insects, damaging stored grains. Agrobacterial LPS elicits insect mortalities comparable to Permethrin (standard insecticide). Typical strains (At2, At3 At5, At6) incited 80% mortality of tested insects. EPS yield was quantified at regular intervals under varying physical parameters. Maximum EPS yield of 12.25 g/L was recorded for strain At1. Antibacterial activity of all isolates (before and after UV light exposure) was tested against Gram-positive and Gram-negative reference strains. Agrobacteria exposed to UV light exhibited antibacterial activity against Gram-positive reference strains. Therefore, agrobacterial LPS can be future candidate for biocontrol of insect pests in grain stocks. Moreover, agrobacteria can not only be prospective candidates for industrial scale EPS production but can also potentially help in treating infections by antibiotic resistant Gram-positive bacteria. Hence, same native isolates carry numerous benefits for the community.

Radiosynthesis and Biodistribution of 18F-Linezolid in Mycobacterium tuberculosis-Infected Mice Using Positron Emission Tomography.

Oxazolidinones are a novel class of antibacterials with excellent activity against resistant Gram-positive bacteria including strains causing multidrug-resistant tuberculosis (TB). Despite their excellent efficacy, optimal dosing strategies to limit their toxicities are still under development. Here, we developed a novel synthetic strategy for fluorine-18-radiolabeled oxazolidinones. As proof-of-concept, we performed whole-body 18F-linezolid positron emission tomography (PET) in a mouse model of pulmonary TB for noninvasive in situ measurements of time-activity curves in multiple compartments with subsequent confirmation by ex vivo tissue gamma counting. After intravenous injection, 18F-linezolid rapidly distributed to all organs with excellent penetration into Mycobacterium tuberculosis-infected lungs. Drug biodistribution studies with PET can provide unbiased, in situ drug measurements, which could boost efforts to optimize antibiotic dosing strategies.