Toxic Antimicrobial Agents Research Articles

In vitro antimicrobial activity of hydrosol from Litsea cubeba (Lour.) Pers. against Helicobacter pylori and Candida albicans

Introduction: Helicobacter pylori and Candida albicans are classified as the most common pathogenic agents in humans. H. pylori is responsible for gastroduodenal diseases and greatly associated with gastric carcinogenesis, while C. albicans is the main cause of fungal urinary tract, genital yeast, and fungal skin infections. The increasing appearance of drug-resistant strains of H. pylori and C. albicans has made the treatment of the infections more serious. Hydrosols from plant steam distillation have been traditionally used in medicine, cosmetics, and culinary uses. They have been recently suggested as antimicrobial agents owing to their safety and ability to reduce the potential of resistance. The aim of the present study is to assess antibacterial and antifungal activities of hydrosols extracted from the fresh fruits of Litsea cubeba against H. pylori and C. albicans.
 Methods: The L. cubeba fruit hydrosol was obtained by steam distillation method. Evaluation of the growth-inhibiting and microbicidal effects of the hydrosol towards the H. pylori ATCC 43504 and C. albicans ATCC 10231 was determined through MIC (minimal inhibitory concentration), MBC (minimal bactericidal concentration), and MFC (minimal fungicidal concentration) measurements using broth dilution assays. Compositions of the dissolved essential oil (dEO) from the hydrosol were analyzed by GC-MS (gas chromatography-mass spectrometry).
 Results: The results indicated that the L. cubeba fruit hydrosol exhibited strong antimicrobial ability towards the bacterium H. pylori (MIC of 10%, MBC of 30%) and the yeast C. albicans (MIC of 10%, MFC of 40%). The cells of H. pylori and C. albicans were killed completely after 24 and 18 hours of treatment with 30% and 40% of the hydrosol, respectively. The major constituents of the dEO were geranial (32.92%), neral (27.12%), p-menthan-8-yl acetate (8.45%), 2-cyclopropyl-2-methylspiro[2.2]pentane-1-carboxylic acid (8.09%), linalool (4.24%), and methyl heptenone (4.15%).
 Conclusion: The results of the study suggest that L. cubeba fruit hydrosols could be used as potent natural antibacterial and antifungal preparations in the global effort to discover safe alternatives to toxic antimicrobial agents.

Synthesis of VO2/Poly(MMA-co-dMEMUABr) antimicrobial/thermochromic dual-functional coatings

In order to address the need for window coatings that can control room temperature while being self-cleaning, this work examined a dual-functional antimicrobial/thermochromic coating. The goal was addressed by chemically polymerizing the antimicrobial agent, quaternary ammonium compound (QAC) N,N-dimethyl-N-{2-[(2-methylprop-2-enoyl)oxy]ethyl}undecane-1-aminium bromide (dMEMUABr) while using vanadium dioxide (VO2) as the thermochromic agent. The antimicrobial agent dMEMUABr, having an acrylic moiety and a long hydrocarbon tail for enhanced killing, was synthesized and characterized by NMR and FTIR spectroscopies. VO2 nanoparticles were synthesized hydrothermally and characterized by physicochemical analysis including powder XRD, DSC and SEM. Polymer coatings were obtained by polymerizing dMEMUABr with methyl methacrylate (MMA) monomer under UV irradiation with the required UV curing time being investigated. Thermochromic performance of dual-functional VO2/poly(MMA-co-dMEMUABr) coating gave an infrared modulation ΔTIR of 5.8 % and luminous transmittance Tlum of 36.1 % at 25 °C. The antimicrobial testing of the dual-functional coating indicated that it could kill 90.3 % of bacteria Escherichia coli (E. coli) within 24 h at a low dMEMUABr concentration (3.8 wt % relative to MMA). The zone of inhibition test proved the contact kill principle of the coating, without releasing toxic antimicrobial agents to the environment.

Clinical effectiveness of an immunomodulatory drug based on a muramylpeptide composition in the treatment of patients with chronic generalized periodontitis

To assess the efficacy of an immunomodulatory drug based on a muramylpeptide composition in the treatment of patients with chronic generalized periodontitis. The study comprised 40 patients with chronic generalized periodontitis. In controls the treatment consisted in oral hygiene instructions, professional oral hygiene procedures and root scalling while in main study group the conventional treatment protocol was combined with intramuscular injections of muramylpeptide composition. The study showed significant reduction of inflammatory symptoms in periodontal tissues in muramylpeptide composition group. Muramylpeptide composition increases the threshold of tissue protection against constantly present microbial accumulations in periodontal disease patients thus providing opportunity for excluding toxic antimicrobial agents and/or antibiotics (or reducing their dosages).

Enzyme-Immobilized Chitosan Nanoparticles as Environmentally Friendly and Highly Effective Antimicrobial Agents.

Highly effective and minimally toxic antimicrobial agents have been prepared by immobilizing glucose oxidase (GOx) onto biocompatible chitosan nanoparticles (CS-NPs). CS-NPs were prepared via ionotropic gelation and used for the immobilization of GOx via approaches of covalent attachment (CA), enzyme coating (EC), enzyme precipitate coating (EPC), and magnetic nanoparticle-incorporated EPC (Mag-EPC). EPC represents an approach consisting of enzyme covalent attachment, precipitation, and cross-linking, with CA and EC being control samples while Mag-EPC was prepared by mixing magnetic nanoparticles (Mag) with enzymes during the preparation of EPC. The GOx activities of CA, EC, EPC, and Mag-EPC were 8.57, 17.7, 219, and 247 units/mg CS-NPs, respectively, representing 26 and 12 times higher activity of EPC than those of CA and EC, respectively. EPC improved the activity and stability of GOx and led to good dispersion of CS-NPs, while Mag-EPC enabled facile magnetic separation. To demonstrate the expandability of the EPC approach to other enzymes, bovine carbonic anhydrase was also employed to prepare EPC and Mag-EPC samples for their characterizations. In the presence of glucose, EPC of GOx generated H2O2 in situ, which effectively inhibited the proliferation of Staphylococcus aureus in both suspended cultures and biofilms, thereby demonstrating the potential of EPC-GOx as environmentally friendly and highly effective antimicrobial materials.

Graph Theoretical Analysis, In Silico Modeling, Synthesis, Anti-Microbial and Anti-TB Evaluation of Novel Quinoxaline Derivatives.

We designed to synthesize a number of 2-(2-(substituted benzylidene) hydrazinyl)-N-(4-((3-(phenyl imino)-3,4-dihydro quinoxalin-2(1 H)-ylidene)amino) phenyl) acetamide S1-S13: with the hope to obtain more active and less toxic anti-microbial and anti-TB agents. A series of novel quinoxaline Schiff bases S1-S13: were synthesized from o-phenylenediamine and oxalic acid by a multistep synthesis. In present work, we are introducing graph theoretical analysis to identify drug target. In the connection of graph theoretical analysis, we utilised KEGG database and Cytoscape software. All the title compounds were evaluated for their in-vitro anti-microbial activity by using agar well diffusion method at three different concentration levels (50, 100 and 150 µg/ml). The MIC of the compounds was also determined by agar streak dilution method. The identified study report through graph theoretical analysis were highlights that the key virulence factor for pathogenic mycobacteria is a eukaryotic-like serine/threonine protein kinase, termed PknG. All compounds were found to display significant activity against entire tested bacteria and fungi. In addition the synthesized scaffolds were screened for their in vitro antituberculosis (anti-TB) activity against Mycobacterium tuberculosis (Mtb) strain H37Ra using standard drug Rifampicin. A number of analogs found markedly potent anti-microbial and anti-TB activity. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. The observed study report was showing that the compound S6: (4-nitro substitution) exhibited most potent effective anti-microbial and anti-TB activity out of various tested compounds.

Magnetic Extraction of Acinetobacter baumannii Using Colistin-Functionalized γ-Fe2O3/Au Core/Shell Composite Nanoclusters

Acinetobacter baumannii is a Gram-negative bacterium of increasing concern due to its virulence and persistence in combat and healthcare environments. The incidence of both community-acquired and nosocomial A. baumannii infections is on the rise in foreign and domestic healthcare facilities. Treatment options are limited due to the acquisition of multidrug resistance to the few effective antibiotics. Currently, the most effective pharmaceutically based treatment for multidrug-resistant A. baumannii infections is the antibiotic colistin (polymyxin E). To minimize side effects associated with administration of colistin or other toxic antimicrobial agents, we propose the development of a nanotechnology-mediated treatment strategy. In this design-based effort, colistin-functionalized multilayered, inorganic, magnetoplasmonic nanoconstructs were fabricated to bind to the surface of A. baumannii. This result, for the first time, demonstrates a robust, pharmaceutical-based motif for high affinity, composite nanoparticulates targeting the A. baumannii surface. The antibiotic-activated nanomaterials demonstrated cytocompatibility with human cells and no acute bacterial toxicity at nanoparticle to bacterial concentrations <10 000:1. The magnetomotive characteristics of the nanomaterial enabled magnetic extraction of the bacteria. In a macroscale environment, maximal separation efficiencies exceeding 38% were achieved. This result demonstrates the potential for implementation of this technology into micro- or mesofluidic-based separation environments to enhance extraction efficiencies. The future development of such a mesofluidic-based, nanotechnology-mediated platform is potentially suitable for adjuvant therapies to assist in the treatment of sepsis.

English

The development of effective and less toxic antimicrobial agents is required for the treatment of respiratory tract infections. This study was carried out to evaluate the phytochemical and antibacterial activities of Anogeissus leiocarpus (DC.) (Guill. & Perr.) and Terminalia glaucescens (Planch. ex Benth.) against non-tuberculous mycobacteria species. The methanol, dichloromethane and aqueous extracts were screened against five (5) non-tuberculosis mycobacteria (NTM) species by agar diffusion method. Minimum inhibitory concentration (MIC) was determined by agar dilution method while bactericidal studies were done by viable count technique. The methanol and aqueous extracts were active against all the test organisms with zones of inhibition ranging from 10±0.0 to 25±0.5 mm. The MIC and MBC range from 0.3125 to 2.5 and 1.25 to 10 mg/mL, respectively. Bactericidal activities of aqueous extracts against Mycobacterium smegmatis ATCC 19420 revealed a drastic dose-dependent decline in the surviving population after 6 h of exposure accompanied by a total (100%) kill after 24 h of exposure. The antimicrobial activities demonstrated by these plants suggest the presence of therapeutically important antimycobacterial compounds and thus justify as well as support the use of these medicinal plants for the treatment of respiratory tract infections. Key words: Anogeissus leiocarpus (DC.) (Guill. & Perr.), Terminalia glaucescens (Planch. ex Benth.), antibacterial, nontuberculous mycobacteria species, bactericidal, in vitro.

Protein kinase C-δ inhibitor, Rottlerin inhibits growth and survival of mycobacteria exclusively through Shikimate kinase

The molecular bases of disease provide exceptional prospect to translate research findings into new drugs. Nevertheless, to develop new and novel chemical entities takes huge amount of time and efforts, mainly due to the stringent processes. Therefore, drug repurposing is one of such strategies which is being used in recent times to identify new pharmacophores. The essential first step in discovery of the specific inhibitor with low toxicity is the identification and elucidation of pathways exclusive to target pathogen. One such target is the shikimate pathway, which is essential for algae, higher plants, bacteria and fungi. Since, this enzyme system is absent in higher eukaryotes and in mammals, the enzymes involved in the pathway provide an attractive target for the development of potentially selective and non toxic antimicrobial agents. Since, so far there is no specific inhibitor which is able to restrain mycobacterial shikimate pathway; we expanded the use of a known kinase inhibitor; Rottlerin, in order to predict the prototype in discovering the specific molecules against this enzyme. For the first time we have shown that Rottlerin inhibits extracellular mycobacteria by affecting Shikimate Kinase (SK) and this effect is further enhanced during the intracellular infection due to the added effect of PKC- δ down-regulation. The molecular docking of Rottlerin with both the mycobacterial SKs, corroborated the inhibition data, and revealed that the effects of SK, in slow and in fast grower mycobacteria are due to the changes in affinity of binding with the drug.

Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem Resistant Escherichia coli: In Vivo Trials in a Murine Model

The prevalence of Carbapenem Resistant Escherichia coli (CRE) has increased considerably during the last decade, which can be ascribed to relative scarcity of effective non toxic antimicrobial agents. The present study was conducted to evaluate the antimicrobial activity of aquo-ethanolic (1:1) extract of leaves of Camellia sinensis (PTRC-31911-A) against Carbapenem Resistant Escherichia coli at preclinical level using peritonitis infection model in Sprague Dawley rats. Efficacy analysis of PTRC-31911-A involved enumeration of CRE colonies in blood and urine samples of test animals for a period of 5 days from infection. A reduction in microbial count of biological fluids was considered as the primary endpoint of the selected murine model. Physical, biochemical, hematological and histological indices of toxicity were employed as secondary relative indicators of the induced disease. Physical manifestations of infected rats included significantly high body temperature (TempInfected=103.18°F, ∼5% increase) and noteworthy reduction in weight (WeightInfected=126.83g, ∼15% decrease) as compared to control. Significant (P<0.05) increase in total white blood cells, eosinophil and monocyte counts as well as a significant decrease (P<0.05) in erythrocytes count, hematocrit volume, red blood cell distribution width and hemoglobin concentration were observed in the infected group as compared to the control group. Furthermore, noteworthy increase in liver and kidney function test parameters were observed in case of infected groups. All the hematological and biochemical parameters were found to be within optimum range in case of treatment group, indicating restoration of homeostasis. Histopathological studies also presented symptoms of hemorrhage and glomerular damage with structural distortion in glomerular capillary loops of infected groups, which were later recovered in treated groups, indicating the nephro-protective potential of PTRC-31911-A. The study clearly points out that Camellia sinensis extract (PTRC-31911-A; single dose of 5mg/Kg bwt; oral,+24h) is highly effective against Carbapenem Resistant Escherichia coli owing mainly to the presence of flavonoids and polyphenolic compounds, identified by LCMS. Ongoing studies are expected to further unravel the mechanism of action and bioactivity determinants of this broad spectrum plant extract.

Synthesis, characterization and antimicrobial evaluation of some novel 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine bearing substituted phenylquinolin-2-one moiety

Pathogenic microbes have mutated and developed resistance to the latest range of antibiotics, which has kept synthetic chemist hunting for better and least toxic antimicrobial agents. Cyclocondensation of substituted anilines with 3-phenyl-2-propenoic acid yielded Phenyl-(substituted)-quinolin-2-one derivatives (1a–1t). In the next step phenylquinolin-2-one acetic acid derivatives (2a–2t) were prepared by the treatment of (1a–1t) with chloroacetic acid. Further (2a–2t) derivatives were reacted with thiocarbohydrazide to obtain a series of 4-amino-5-sulfanyl-4,5-dihydro-1,2,4-triazolo-4-pheny-(substituted)-quinolin-2-one derivatives (3a–3t). Then condensation of (3a–3t) with phenacyl bromide provided series of fused heterocyclic derivatives of 4-phenyl-1-({6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl}methyl)-(substituted)-1,2-dihydro quinolin-2-one (4a–4t). Structures of these newly synthesized derivatives were established by elemental analysis, FT-IR, 1H NMR and Mass spectroscopy. Final derivatives (4a–4t) were screened for their in vitro antibacterial and antifungal activities against the standard drugs Ampicillin and Fluconazole respectively. The compounds 4d, 4g and 4j showed potent activity against all the studied microbes. Particularly compounds substituted with halogen groups at para position of phenylquinoline ring exhibited significant antimicrobial activity against studied microbes.

Antimicrobial Activity of Some Plant and Algal Extracts

The use of advanced, effective and less toxic antimicrobial agents are required for the treatment of plant pathogens. In this study, hexane and ethanol extracts of two plants (Sesbania sesban and Cymbopogon citratus) and two algae species (Spirulina platensis and Scendusmus sp.) were screened for their antifungal and antibacterial activity on eight fungi (Rhizoctonia solani, Rhizopus stolonifer, Fusarium oxysporum, Aspergillus niger, Alternaria solani, Pythium debarianum, Botrytis cinerea and Penicillium digitatum) and two species of bacteria (Agrobacterium tumefaciens and Erwinia carotovora var. carotovora). Extracts of these plants and algae showed varied levels of antifungal and antibacterial activity. It was found that, the ethanol extracts of S. sesban plant and S. platensis alga had a high activity on tested fungi. On the other hand, the ethanol extracts of Scendesmus sp. alga and S. sesban plant showed the highest antibacterial activity against tested bacteria. The ethanol extract of S. sesban was the most potent fungitoxic extract against both A. niger and A. solani fungi with effective concentration (EC50) values of 0.135 and 0.011mg/L, respectively. On contrary, Scendesmus sp. ethanol extract revealed the highest inhibitory effect against E. carotovora var. carotovora bacteria. Conference Proceeding Full Paper Abbassy et al.; IJPSS, Article no. IJPSS.2014.10.014 1367

Antisense RNA regulation and application in the development of novel antibiotics to combat multidrug resistant bacteria.

Despite the availability of antibiotics and vaccines, infectious diseases remain one of most dangerous threats to humans and animals. The overuse and misuse of antibacterial agents have led to the emergence of multidrug resistant bacterial pathogens. Bacterial cells are often resilient enough to survive in even the most extreme environments. To do so, the organisms have evolved different mechanisms, including a variety of two-component signal transduction systems, which allow the bacteria to sense the surrounding environment and regulate gene expression in order to adapt and respond to environmental stimuli. In addition, some bacteria evolve resistance to antibacterial agents while many bacterial cells are able to acquire resistance genes from other bacterial species to enable them to survive in the presence of toxic antimicrobial agents. The crisis of antimicrobial resistance is an unremitting menace to human health and a burden on public health. The rapid increase in antimicrobial resistant organisms and limited options for development of new classes of antibiotics heighten the urgent need to develop novel potent antibacterial therapeutics in order to combat multidrug resistant infections. In this review, we introduce the regulatory mechanisms of antisense RNA and significant applications of regulated antisense RNA interference technology in early drug discovery. This includes the identification and evaluation of drug targets in vitro and in vivo, the determination of mode of action for antibiotics and new antibacterial agents, as well as the development of peptide-nucleic acid conjugates as novel antibacterials.

Review of the Sulfonamides and Trimethoprim

Review of the Sulfonamides and Trimethoprim

The Aminoglycosides

Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides continue to serve a useful role in the treatment of serious enterococcal, mycobacterial, and gram-negative bacillary infections. Gentamicin, because of its low cost, remains the aminoglycoside of choice in hospitals with low levels of resistance among Enterobacteriaceae and Pseudomonas aeruginosa. Typically, it is administered in combination with β-lactam antibiotics, but it may also be used as monotherapy for urinary tract infections or tularemia. Amikacin is useful against gentamicin-resistant gram-negative bacilli and also in the treatment of infections caused by susceptible Nocardia and nontuberculous mycobacteria. Streptomycin serves an important role in the treatment of multidrug-resistant tuberculosis and may be useful in the treatment of some gentamicin-resistant enterococcal infections. Despite an alarming increase in aminoglycoside-resistant enterococci, most institutions have noted little change in patterns of resistance among gram-negative bacilli. Although the development of newer, less toxic aminoglycosides is unlikely in the near future, single daily dosing regimens have been proposed as a convenient, cost-effective strategy. In selected patients, this novel approach seems to be as safe and effective as traditional, multidose regimens. Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides continue to serve a useful role in the treatment of serious enterococcal, mycobacterial, and gram-negative bacillary infections. Gentamicin, because of its low cost, remains the aminoglycoside of choice in hospitals with low levels of resistance among Enterobacteriaceae and Pseudomonas aeruginosa. Typically, it is administered in combination with β-lactam antibiotics, but it may also be used as monotherapy for urinary tract infections or tularemia. Amikacin is useful against gentamicin-resistant gram-negative bacilli and also in the treatment of infections caused by susceptible Nocardia and nontuberculous mycobacteria. Streptomycin serves an important role in the treatment of multidrug-resistant tuberculosis and may be useful in the treatment of some gentamicin-resistant enterococcal infections. Despite an alarming increase in aminoglycoside-resistant enterococci, most institutions have noted little change in patterns of resistance among gram-negative bacilli. Although the development of newer, less toxic aminoglycosides is unlikely in the near future, single daily dosing regimens have been proposed as a convenient, cost-effective strategy. In selected patients, this novel approach seems to be as safe and effective as traditional, multidose regimens.

The Aminoglycosides

Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides continue to serve a useful role in the treatment of serious enterococcal, mycobacterial, and gram-negative bacillary infections. Gentamicin, because of its low cost, remains the aminoglycoside of choice in hospitals with low levels of resistance among Enterobacteriaceae and Pseudomonas aeruginosa. Typically, it is administered in combination with beta-lactam antibiotics, but it may also be used as monotherapy for urinary tract infections or tularemia. Amikacin is useful against gentamicin-resistant gram-negative bacilli and also in the treatment of infections caused by susceptible Nocardia and nontuberculous mycobacteria. Streptomycin serves an important role in the treatment of multidrug-resistant tuberculosis and may be useful in the treatment of some gentamicin-resistant enterococcal infections. Despite an alarming increase in aminoglycoside-resistant enterococci, most institutions have noted little change in patterns of resistance among gram-negative bacilli. Although the development of newer, less toxic aminoglycosides is unlikely in the near future, single daily dosing regimens have been proposed as a convenient, cost-effective strategy. In selected patients, this novel approach seems to be as safe and effective as traditional, multidose regimens.

Enhancement of the effectiveness of antimicrobial therapy by muramyl peptide immunomodulators.

Besides promoting nonspecific resistance to experimental infection, muramyl peptide immunomodulators also potentiate the effects of antimicrobial agents. These substances have been evaluated in combination with appropriate anti-infective agents in various models of bacterial, fungal, parasitic, and viral infection. For the combined regimens to be effective, the immunomodulator apparently must be administered prophylactically; anti-infective efficacy is then increased in situations where the muramyl peptide is capable of promoting at least some resistance to the infection independent of the antimicrobial agent. Adjunctive administration of the muramyl peptide may reduce the required dosages of potentially toxic antimicrobial agents and hence may lower the risk of toxic side effects. Because of the way in which they stimulate the inflammatory/immune systems, muramyl peptide immunomodulators may improve the outcome of therapy for infections in immunocompromised hosts. Initial clinical applications could involve the use of these immunomodulators in combination with antimicrobial agents as prophylaxis in high-risk individuals without overt infections.

The Aminoglycosides

Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides continue to serve a useful role in the treatment of serious enterococcal and gram-negative bacillary infections. Gentamicin, because of its low cost, remains the aminoglycoside of choice in hospitals with low levels of resistance among Enterobacteriaceae and Pseudomonas aeruginosa. Amikacin is useful against gentamicin-resistant gram-negative bacilli and also in the treatment of infections caused by susceptible Nocardia and nontuberculous mycobacteria. An alarming increase in resistance to aminoglycosides among enterococci has been noted, despite little change in susceptibility patterns among gram-negative bacilli. Future efforts will need to be directed toward a better understanding of mechanisms of antimicrobial resistance and toward the prevention of aminoglycoside-induced toxicity.

Effects of antimicrobial agents on growth and chemotaxis of Trichomonas vaginalis.

The motility of viable Trichomonas vaginalis organisms is readily demonstrable in a clinical wet mount or cultured specimens. We attempted to determine whether migration is a dynamic process such that the organisms move to avoid exposure to toxic antimicrobial agents. With the use of axenic cultures of T. vaginalis that were radiolabeled and assayed for chemotaxis in plastic multiwelled plates with a membrane filter inserted to trap organisms, the response of clinical isolates to various antimicrobial agents was studied. Chemotaxis was readily demonstrable and dependent upon factors including time of incubation, media used, and viscosity of media. Nitroimidazoles (e.g., metronidazole) which readily inhibited the growth of these organisms also caused significant chemorepulsion after minutes of exposure. The antifungal imidazoles ketoconazole and miconazole inhibited growth nearly as readily and caused chemorepulsion, but to a lesser degree. The spermicide Nonoxynol-9 also inhibited growth and caused significant chemorepulsion. The minimal concentrations of many compounds which inhibited growth were very similar to those which caused significant chemorepulsion. Imidazole and antibiotics (e.g., penicillin) which did not inhibit growth did not induce any chemotactic effects. Chemotaxis of T. vaginalis is an active and dynamic process, and the organisms display chemorepulsion shortly after exposure to toxic antimicrobial agents, well before toxicity can be demonstrated.

The Aminoglycosides: Streptomycin, Kanamycin, Gentamicin, Tobramycin, Amikacin, Netilmicin, and Sisomicin

Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides remain useful in the treatment of serious, hospital-acquired, gram-negative bacillary infections, especially those caused by Pseudomonas aeruginosa. Formidable nephrotoxicity and ototoxicity have limited the use of neomycin to topical or oral administration. Widespread antimicrobial resistance among Enterobacteriaceae has restricted the use of streptomycin and kanamycin to a few specific clinical situations. Gentamicin, tobramycin, and amikacin are active against a wide range of Enterobacteriaceae and many P. aeruginosa organisms. In medical centers where gentamicin resistance is prevalent, amikacin is the aminoglycoside of choice. Fortunately, amikacin resistance has not seemed to increase substantially, even in institutions where usage has been extensive for a long period. No new aminoglycoside has proved to be superior to amikacin.

Use the Passive Voice!

Many medical writers hold dear and cite often the advice quoted above. However, in their zeal to obey they neglect to notice that like all advice (Buy tax-free municipal bonds!), it is appropriate in some cases than in others. They also fail to acknowledge that the esteemed authorities Strunk and White advise use of the passive voice when suitable, ie, in a good deal of medical writing. The sulfonamides have been largely replaced by effective and less toxic antimicrobial agents... 2 Since the subject of discussion is sulfonamides, it seems more direct and vigorous to let the subject of the sentence be sulfonamides also, rather than turning it around to read: More effective and less toxic antimicrobial agents have largely replaced the sulfonamides... Rabbits sick with tularemia are easily caught by dogs or cats and may, therefore, be brought into contact with human beings. 3 The author