Addition Of Antibacterial Agents Research Articles

Lefamulin for Mycoplasma genitalium treatment failure in Australia and the USA: a case series and pilot open-label parallel arm randomised trial

ObjectivesMycoplasma genitalium (MG) causes urethritis and is associated with cervicitis, pelvic inflammatory disease and preterm delivery. Antimicrobial resistance is widespread and cure rates are declining. Lefamulin, a novel pleuromutilin, may...

Antimicrobial surveillance: A 20-year history of the SMART approach to addressing global antimicrobial resistance into the future

Antimicrobial resistance (AMR) is a major global public health threat, particularly affecting patients in resource-poor settings. Comprehensive surveillance programmes are essential to reducing the high mortality and morbidity associated with AMR and are integral to informing treatment decisions and guidelines, appraising the effectiveness of intervention strategies, and directing development of new antibacterial agents. Various surveillance programmes exist worldwide, including those administered by government bodies or funded by the pharmaceutical industry. One of the largest and longest running industry-sponsored AMR surveillance programme is the Study for Monitoring Antimicrobial Resistance Trends (SMART), which recently completed its 20th year. The SMART database has grown to almost 500000 isolates from over 200 sites in more than 60 countries, encompassing all major geographic regions and including many sites in low- and middle-income countries. The SMART surveillance programme has evolved in scope over time, including additional antibacterial agents, pathogens and infection sites, in line with changing epidemiology and medical need. Surveillance data from SMART and similar programmes have been used successfully to detect emerging resistance threats and AMR patterns in specific countries and regions, thus informing national and local clinical treatment guidelines. The SMART database can be accessed readily by physicians and researchers globally, which may be especially valuable to those from countries with limited healthcare resources, where surveillance and resistance data are rarely collected. Continued participation from as many sites as possible worldwide and maintenance of adequate funding are critical factors to fully realising the potential of large-scale AMR surveillance programmes into the future.

AEROBIC VAGINITIS (AV): DISEASE BURDEN, BACTERIOLOGICAL PROFILE AND ANTIMICROBIAL SUSCEPTIBILITY PATTERN IN WESTERN MAHARASHTRA

Vaginitis is a very common and recurrent infection in reproductive age group especially worrisome in pregnant females. If it is misdiagnosed, left untreated or wrongly treated can lead to serious complications. With this background present study was conducted to determine the prevalence, bacteriological profile and antimicrobial susceptibility of the pathogens causing aerobic vaginitis. Study was conducted over a period of 1year in which 241 vaginal swabs were processed for aerobic culture and gram stain. The organisms were identified and antimicrobial susceptibility was performed by Vitek 2 compact system. Out of 241 samples processed 37(15.4%) showed bacterial growth. S. aureus (40.5%), GBS (13.5%), E. coli (13.5%) and K. pneumoniae (13.5%) were the common pathogens isolated. Gram positive organisms showed highest sensitivity to Vancomycin and Linezolid. All gramnegative bacteria were sensitive to Imipenem and Meropenem. This study recommends the laboratory-based diagnosis of each clinically suspected case of vaginitis for appropriate management of patient. Addition of antibacterial agent in traditional empirical antifungal therapy for vaginitis is need of hour

Preparation, Characterization and Antibacterial Property Analysis of Cellulose Nanocrystals (CNC) and Chitosan Nanoparticles Fine-Tuned Starch Film

To improve the mechanical and antibacterial properties of traditional starch-based film, herein, cellulose nanocrystals (CNCs) and chitosan nanoparticles (CS NPs) were introduced to potato starch (PS, film-forming matrix) for the preparation of nanocomposite film without incorporation of additional antibacterial agents. CNCs with varied concentrations were added to PS and CS NPs composite system to evaluate the optimal film performance. The results showed that tensile strength (TS) of nanocomposite film with 0, 0.01, 0.05, and 0.1% (w/w) CNCs incorporation were 41, 46, 47 and 41 MPa, respectively. The elongation at break (EAB) reached 12.5, 10.2, 7.1 and 13.3%, respectively. Due to the reinforcing effect of CNCs, surface morphology and structural properties of nanocomposite film were altered. TGA analysis confirmed the existence of hydrogen bondings and electrostatic attractions between components in the film-forming matrix. The prepared nanocomposite films showed good antibacterial properties against both E. coli and S. aureus. The nanocomposite film, consist of three most abundant biodegradable polymers, could potentially serve as antibacterial packaging films with strong mechanical properties for food and allied industries.

A Highly Efficient Polystyrene-Based Cationic Resin to Reduce Bacterial Contaminations in Water

Nowadays, new water disinfection materials attract a lot of attention for their cost-saving and ease of application. Nevertheless, the poor durability of the matrices and the loss of physically incorporated or chemically attached antibacterial agents that can occur during water purification processes considerably limit their prolonged use. In this study, a polystyrene-based cationic resin (R4) with intrinsic broad-spectrum antibacterial effects was produced without needing to be enriched with additional antibacterial agents that could detach during use. Particularly, R4 was achieved by copolymerizing 4-ammonium-butyl-styrene (4-ABSTY) with N,N-dimethylacrylamide (DMAA) and using N-(2-acryloylamino-ethyl)-acrylamide (AAEA) as a cross-linker. The R4 obtained showed a spherical morphology, micro-dimensioned particles, high hydrophilicity, high-level porosity, and excellent swelling capabilities. Additionally, the swollen R4 to its maximum swelling capability, when dried with gentle heating for 3 h, released water following the Higuchi's kinetics, thus returning to the original structure. In time-kill experiments on the clinical isolates of multidrug-resistant (MDR) pathogens of fecal origin, such as enterococci, Group B Salmonella species, and Escherichia coli, R4 showed rapid bactericidal effects on enterococci and Salmonella, and reduced E. coli viable cells by 99.8% after 4 h. When aqueous samples artificially infected by a mixture of the same bacteria of fecal origin were exposed for different times to R4 in a column, simulating a water purification system, 4 h of contact was sufficient for R4 to show the best bacterial killing efficiency of 99%. Overall, thanks to its physicochemical properties, killing efficiency, low costs of production, and scalability, R4 could become a cost-effective material for building systems to effectively reduce bacterial, even polymicrobial, water contamination.

Injectable, Intrinsically Antibacterial Conductive Hydrogels with Self-Healing and pH Stimulus Responsiveness for Epidermal Sensors and Wound Healing.

Torealize intelligent and personalized medicine, it is a huge challenge to develop a hydrogel dressing that can be used as a sensor to monitor human health in real-time while promoting wound healing. Herein, an injectable, self-healing, and conductive chitosan-based (CPT) hydrogel with pH responsiveness and intrinsic antibacterial properties was fabricated via a Schiff base linkage and a hydrogen bond. Due to the introduction of Schiff base bonds, the injectable CPT hydrogel exhibits various excellent properties, such as pH responsiveness to sol-gel transition, self-healing properties, and broad-spectrum antibacterial properties even without additional antibacterial agents. In vitro experiments verify the excellent biocompatibility of the as-prepared hydrogel. An in vivo experiment in a mouse full-thickness skin-wound model was performed to confirm the outstanding effect on wound healing. Meanwhile, as epidermal sensors, the conductive hydrogel that perceives various human activities in real-time could provide the real-time analysis of the patient's healthcare information. Based on these excellent properties, the CPT hydrogel, as a biological dressing with a sensing function, lays a solid foundation for the further realization of personalized medicine.

Application of Partial Hydrolysis of Virgin Coconut oil (VCO) on Carrageenan-based Edible Coatinng as (Sphyraena barracuda) Fishball Preservative during Room Storage

Food spoilage during storage occurs physically, chemically and biologically which is related to the activity of bacteria. One of the natural preservation that is currently developing is the application of edible coating on perishable food, such as fishball. Addition of antibacterial agent is important to improve edible coating. Virgin coconut oil contains medium chain fatty acids which have antimicrobial properties, particularly monoglycerides and free fatty acids that produced by hydrolyzing partially triglycerides at the Sn-1 and Sn-3 position using Lipozyme. The aim of this research was to test the effect of edible coating carrageenan enriched with virgin coconut oil hydrolysis (HVCO) (concentrations 1%,3%,5%) on fishball quality.The method was an experimental with factorial completely randomized design.The samples were analyzed for sensorial assessments, Total plate Count, Total Volatile Base-Nitrogen, Water content, and pH for 5 days at room temperature. The study demonstrated that fish meatball coated with carrageenan based-edible coating fortified with HVCO showed the best result compared to controls (Uncoated fishball, coated without HVCO). Sensory attributes were still accepted by panelists until 3 days. Meanwhile, the same pattern depicted by TPC and TVB-N parameters. HVCO5% had inhibited microbial growth and retarded the increase of TVB-N number on fishball, the results were Log 5,08cfu/gr, 29,69 mg/100 gr respectively.

Comparative Evaluation of Antibacterial Effects of Nanoparticle-Incorporated Orthodontic Primer: An In Vitro Study

Aim and Objectives: To compare and evaluate the antibacterial efficacy of various nanoparticles incorporated in orthodontic primer with that of conventional antimicrobial agents at different concentrations on Streptococcus mutans ( S. mutans) strain. Materials and Methods: Transbond XT Primer was mixed with 2.5% and 5% benzalkonium chloride (BAC), 0.2% and 2.5% chlorhexidine, 1% and 3% titanium dioxide (TiO2) nanoparticles, 0.2% and 0.5% nanohydroxyapatite, and 0.2% and 0.5% silica-doped nanohydroxyapatite powders. Antibacterial activity against S. mutans for all the materials was evaluated by the disk diffusion method for periods of 48 (T1) and 72 (T2) hours. Results: There was a significant increase in the antimicrobial activity of the orthodontic primer modified by the addition of antibacterial agents. The highest zone of inhibition against S. mutans was observed for silica-doped nanohydroxyapatite of 0.5% (11.03 mm) among all the nanoparticles, which was similar to the conventional antibacterial agents used in our study. Conclusions: • Among all the groups, BAC at 5% concentration showed the highest antimicrobial activity, and the least activity was exhibited by 1% TiO2 nanoparticles. • Silica-doped nanohydroxyapatite at 0.5% expressed the greatest antibacterial activity among all the nanoparticles. • All the materials showed sustained antibacterial activity even after 72 hours.

Polylactic acid (PLA): Improve it, use it, and dump it faster

Today, many people enjoy an easy lifestyle. However, this comfort has come with a price because of plastic that is thrown away after a single use. As such, governments around the world have pushed for biodegradable plastics to be produced, especially for food packaging, and these can be easily seen in supermarkets, for example. Using plastic for only one time has resulted in environmental pollution. To solve this problem, polylactic acid (PLA) has been introduced as an alternative bio-based plastic to replace artificial petroleum-based plastics. PLA comes from renewable resources and is biodegradable under certain conditions. Furthermore, the development of the properties of PLA could solve problems related to its weakness in packaging applications. This editorial proposes expansion of the property attributes of PLA to include hygienic character, through the addition of antibacterial agents. This can be done by introducing two alternative approaches for waste management: PLA recycling and degradation. However, some key research is still needed to improve the properties and waste management of PLA relative to the effectiveness of its reprocessing and acceleration of its (bio)degradation.

Biocompatible and antibacterial gelatin-based polypyrrole cryogels

Polypyrrole-gelatin cryogels were synthesized by oxidative cryopolymerization of pyrrole in the presence of gelatin. Vibrational spectroscopy confirmed formation of doped polypyrrole. Mechanical and pore structure stability of the resulting macroporous materials (pore size 10–50 μm) was shown to increase with increasing of gelatin content in initial polymerization medium, reaching plateau at 6 wt%. Thermal stability of polypyrrole-gelatin cryogels was found to be enhanced in comparison to its individual components. Electrical conductivity of all prepared cryogels (2–5 S cm−1) was similar to that of conventional polypyrrole. Cytotoxicity of polypyrrole-gelatin cryogels was found to decrease with increasing of gelatin concentration in the initial reaction mixture. The cryogel obtained using 8 wt% of gelatin showed the lowest cytotoxic effect reaching only mild cytotoxicity at 100% extract concentration. Polypyrrole-gelatin gels showed significant level of antibacterial activity without additional antibacterial agents.

Titanium Incorporation into Zr-Porphyrinic Metal-Organic Frameworks with Enhanced Antibacterial Activity against Multidrug-Resistant Pathogens.

This study uses metal-organic frameworks (MOFs) alone without any added antibacterial ingredients as the nonantibiotic agent for photodynamic therapy (PDT) of chronic wounds infected by multidrug-resistant (MDR) bacteria. Nanoparticles (NPs) of MOFs (PCN-224) are incorporated with titanium through a facile cation exchange strategy. The obtained bimetallic PCN-224(Zr/Ti) shows greatly enhanced photocatalytic performance for the generation of reactive oxygen species under visible light, which is responsible for the effective antibacterial activities. The PCN-224(Zr/Ti) NPs are loaded onto lactic-co-glycolic acid nanofibers to prepare a wound dressing, which shows high biocompatibility and minimal cytotoxicity. The wound dressing is efficient for PDT-based in vivo healing of the chronic wound infected by MDR bacteria. Most importantly, this work does not involve any additional antibacterial agents, which is facile, low cost, and in particular, greatly explores the potential of MOFs as a powerful nonantibiotic agent in PDT.

Robust Low Friction Antibiotic Coating of Urethral Catheters Using a Catechol-Functionalized Polymeric Hydrogel Film

Indwelling urethral catheters are widely used in hospitalized patients however they are associated with bacterial infection and biofilm formation due to the suboptimal surface properties of the elastic materials used for the catheters. Although there are several antibacterial coating technologies to modify the surface properties of the catheter including hydrophilic polymeric coating, the risk of infection is still high given the absence of reactive functional groups on the surface of elastomers. In this study, we describe the use of catechol-functionalized hydrophilic polymers and explore strategies to create antibacterial hydrogel coatings. Three different types of catechol-functionalized polymers, chitosan, hyaluronic acid, and human serum albumin were synthesized and deposited using simple dip-coating method. All of the tested polymers could coat different types of elastomers widely used for urethral catheters independent to the surface properties, and the thickness of the coating could be controlled by the number of depositions. The coating formed stable water-containing lubricant surface beneficial as a physical repellant of microbial attachment. In addition, the coating could be combined with additional antibacterial agents such as silver nanoparticles to maximize the antibacterial effect on the surface of urethral catheter materials.

Antibacterial Ability of Mesoporous Carbonated Hydroxyapatite

Mesoporous carbonated hydroxyapatite (Meso-CHA) is a bioceramic materials that offer good biocompatibility and bioactivity properties that suitable for bone defects or diseases treatment and therapy. Antibacterial study is very important to ensure that materials is biocompatible enough to be used on or inside the human body. The aim of this study is to investigate the antibacterial ability of the Meso-CHA (without addition of antibacterial agents) towards Escherichia coli (E. coli) bacteria. Meso-CHA samples were synthesized using chemical precipitation method where surfactant P-123 was used to introduce pores within nanoparticles structure. X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) analysis proved that pure phase of Meso-CHA was obtained. Synthesized Meso-CHA demonstrated higher pore properties (surface area = 146.92 m2g−1, pore size = 2.35 nm, and pore volume = 0.2437 cm3g−1) compared to commercial HA (surface area = 7.84 m2 g−1, pore size = 2.05 nm, and pore volume = 0.0085 cm3 g−1). The antibacterial study demonstrated that Meso-CHA has low antibacterial properties with Minimum Inhibitory Concentration (MIC) of 200 mg.ml−1 compared to HA. Carbonate ion addition into the Meso-CHA structure does not improve the antibacterial ability of the materials.

Impact of cumulative steroid dose on infectious diseases after allogenic hematopoietic stem cell transplantation.

Systemic steroid is used to treat various transplant-related complications after allogenic hematopoietic stem cell transplantation (allo-HSCT). However, measures to evaluate its impact on infections are still limited. Hence, we examined the cumulative steroid dose used within 30days after transplant as a predictor of future risk of infections. This study included 226 patients who underwent their first allo-HSCT at Kyoto University Hospital between 2005 and 2015. Sixty-one patients received transplantation from related donors, 106 received unrelated BMT and 59 received unrelated single-unit CBT. Patients were categorized into three groups according to the cumulative steroid dose in terms of prednisolone: no-steroid group (n=174), low-dose group (≤7mg/kg) (n=22) and high-dose group (>7mg/kg) (n=30). In a multivariate analysis, high-dose steroid administration was associated with cytomegalovirus (CMV) antigenemia (HR 1.91, P=0.037) and bacteremia (HR 2.59, P=0.053). No impact was found on the occurrence of invasive fungal infection. High-dose cumulative steroid could predict high risks of bacteremia and CMV antigenemia. Additional anti-bacterial agents for fever and regular measurement of CMV antigen are recommended for whom with systemic steroid administration even after neutrophil engraftment.

Preparation and Characterization of Antibacterial Nylon 6 Fiber

Due to its excellent mechanical property, dye ability and skin affinity, PA6 has been widely used in apparel, home textiles, military products, etc. However, PA6 fiber is easy to breed bacteria and corroded by bacteria in humid environment. One of development tendency of functional PA6 fiber is to design and develop nylon 6 fiber with excellent antibacterial properties, which is also the research target of this paper. In the present investigation, ZnO antibacterial agent was prepared through sol-gel method, and antibacterial masterbatch was acquired via blending antibacterial agent with PA6 using a twin-screw, then antibacterial PA6 fiber was obtained through melt spinning. The thermal properties, crystallization property of antibacterial PA6 masterbatch were discussed. The effect of drawing ratio on fiber strength, elongation of break, orientation and crystallization was also investigated. The antibacterial properties of antibacterial agent and antibacterial PA6 fiber was analyzed by agar diffusion method. The results of Differential Scanning Calorimetry (DSC) suggests that the antibacterial agent causes the rise of crystallization temperature and crystallization rate. X-Ray Diffraction (XRD) and mechanical testing results reveal that the higher drawing ratio leads to higher orientation and strength of PA6 fiber, lower elongation at break. The addition of antibacterial agent increases the degree of orientation and crystallization, reduces the strength of fiber and tends to form α crystalline in PA6 fiber. Antibacterial tests show that antibacterial PA6 fiber has a good antibacterial performance against Staphylococcus aureus.

Antibacterial Effect and Physical-Mechanical Properties of Temporary Restorative Material Containing Antibacterial Agents.

Introduction. For the maintenance of the aseptic chain created during the treatment the coronal sealing becomes paramount. Aim. Evaluating the antibacterial effect and the physical-mechanical properties of a temporary restorative material containing different antibacterial agents. Material and Methods. Two antibacterial agents (triclosan and chloramine T) were manually added to a temporary restorative material used as base (Coltosol). The antibacterial action of the material was analyzed using the agar diffusion method, in pure cultures of Escherichia coli (ATCC BAA-2336) and Staphylococcus aureus (ATCC 11632) and mixed culture of saliva collection. The microleakage rate was analyzed using bovine teeth, previously restored with the materials, and submitted to thermocycling, in a solution of 0.5% methylene blue, for a period of 24 hours. The physical and mechanical properties of the materials analyzed were setting time, water sorption, solubility, and compression strength. Results. No marginal leakage was observed for all groups. There was no statistical significant difference in antimicrobial activity, setting time, water sorption, solubility, and compression strength among the materials. Conclusion. The addition of antibacterial agents on a temporary restorative material did not optimize the antibacterial ability of the material and also did not change its physical-mechanical properties.

Comparative evaluation of antimicrobial and physical properties of a newer dentin bonding agent with cetylpyridinium chloride: An in vitro study

Context: Though adhesive systems in restorative dentistry possess many advantages, secondary caries is still a problem to be contended with. Addition of antibacterial agents could possibly be a potential remedy for this recurring problem. Aims: To evaluate and compare in vitro the antimicrobial property, microleakage, and shear bond strength of G-Bond (one component self-etching light cured adhesive) with different concentrations of cetylpyridinium chloride (CPC). Settings and Design: In vitro intergroup experimental randomized control trial. Subjects and Methods: The in vitro study with the study groups Group I: G-Bond, Group II: G-Bond with 1% CPC, and Group III: G-Bond with 3% CPC was tested against the clinical isolates of Streptococcus mutans through the direct contact test determining the turbidometric bacterial growth using spectrophotometer. The microleakage was tested using dye penetration method and the shear bond strength of the three groups was tested using universal testing machine. Statistical Analysis Used: The data were analyzed using paired t-test, one-way ANOVA, followed by post-hoc Tukey's test. For all the tests, a P ≤ 0.05 was considered for statistical significance. Results: G-bond with 3% CPC showed the highest rate of antibacterial activity against S. mutans than other two groups (highly significant P < 0.001). However, microleakage and shear bond strength between the groups did not show any statistically significant change. Conclusions: G-Bond with 3% CPC additive was effective against S. mutans.

Antimicrobial performance and the cure and mechanical properties of peroxide‐cured silicone rubber compounds

Nanosilver colloid, Ag‐based zeolite compound, and 2‐hydroxypropyl‐3‐piperazinylquinolinecarboxylic acid methacrylate (HPQCAM) were used as antimicrobial agents and/or mechanical property improvers in peroxide‐cured silicone rubber vulcanizates. The vulcanizates were prepared by using a two‐roll mill followed by a hydraulic press in order to vulcanize the rubber compounds, and their cure characteristics, mechanical properties, and antibacterial performance were assessed. The antimicrobial performance of the silicone rubber compounds was examined through plate‐count‐agar and drop‐plate‐agar methods, as well as the halo test. The results suggested that the addition of all of the antimicrobial agents slightly increased the cure time, except for the Ag‐based zeolite. The addition of all of the antimicrobial agents also affected the mechanical properties of the rubber vulcanizates. The Ag‐based zeolite gave the silicone rubber compound with the most improved mechanical properties, whereas HPQCAM was the most effective antimicrobial agent, as determined by the occurrence of the inhibition zone and 99% reductions of Staphylococcus aureus and Escherichia coli. The changes in silicone rubber surface with the addition of antibacterial agent were shown by progressive decreases in water contact angle. This result was observed only for the HPQCAM agent and was associated with diffusion and the releasing mechanism of the HPQCAM to kill the bacteria. The optical lightness of the silicone vulcanizates decreased with increasing nanosilver content but increased with increasing amounts of Ag‐based zeolite or HPQCAM. J. VINYL ADDIT. TECHNOL., 19:113–122, 2013. © 2013 Society of Plastics Engineers

Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and vancomycin and the interaction between tigecycline and antifungals

Despite growing data on antimicrobial lock therapy (ALT) in treating bacterial catheter-related bloodstream infections (CR-BSIs), ALT has not been established as a treatment option for CR-BSI caused by Candida albicans. Based on our finding that high-dose doxycycline exhibited antifungal activity against mature C. albicans biofilms, we evaluated additional antibacterial agents with Gram-positive activity [azithromycin, tigecycline (TIG) and vancomycin]. After screening these antibiotics, it was found that TIG had substantial antifungal activity against mature C. albicans biofilms. Therefore, TIG was assayed alone and in combination with fluconazole (FLC), amphotericin B (AmB) or caspofungin (CAS). TIG at 2048 μg/mL resulted in a >50% reduction in the growth of planktonic C. albicans cells. TIG inhibited the formation of biofilms from 128 μg/mL. Against mature biofilms, 2048 μg/mL TIG reduced metabolic activity by 84.2%. Furthermore, addition of 512 μg/mL TIG to FLC at all concentrations tested provided additional reduction in the metabolic activity of mature biofilms. However, this was not superior to 512 μg/mL TIG alone. TIG at 512 μg/mL increased the antifungal effect of lower concentrations of AmB (0.03125–0.25 μg/mL), but at 0.03125 μg/mL and 0.0625 μg/mL this effect was not superior to 512 μg/mL TIG alone. TIG inhibited the antifungal effect of higher concentrations of AmB (≥2 μg/mL). TIG at 512 μg/mL inhibited the antifungal activity of CAS at lower concentrations (0.25–8 μg/mL). These data indicate that high-dose TIG is highly active in vitro against planktonic cells, forming biofilms and mature biofilms of C. albicans.

ChemInform Abstract: Microbial Resistance: Novel Screens for a Contemporary Problem

Historically, natural products have been the source of a large variety of antibacterial agents. In the 1980s, no additional useful antibacterial agents were discovered, leading to the belief that most useful chemotypes from natural product sources had already been discovered. At this time, advances in biotechnology made it feasible to produce sufficient enzyme to set up cell-free screens. Chemical compound libraries and combinatorial synthesis became the source of chemical diversity for the screens. In spite of these efforts, very few new antibacterial agents have been discovered in the last decade. At Small Molecule Therapeutics, Inc., we have developed phenotype-based screens that take advantage of the natural physiology and biochemistry of the target enzymes. We have developed a screen to identify bacterial DNA gyrase and topoisomerase IV poisons. The “hits” identified in this screen are being characterized further. A second screen has also been developed against bacterial topoisomerase 1 in which compounds that cause DNA damage through their interaction with bacterial topoisomerase 1 have been identified. Three of the compounds identified in the screen inhibit DNA relaxation mediated by bacterial topoisomerase 1, induce DNA cleavage, are noncytotoxic at >10μM, and have MICs of 4.0 μg/mL against Staphylococcus aureus. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 6, 559–568, 1999