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136481. In vitro antibacterial activities of phloxine B and other halogenated fluoresceins against methicillin-resistant Staphylococcus aureus. Full Text available with Trip Pro

In vitro antibacterial activities of phloxine B and other halogenated fluoresceins against methicillin-resistant Staphylococcus aureus. Fluorescein dyes in which the benzoic acid moiety has been tetrachlorinated (50 to 100 micro g/ml) inhibit in vitro Staphylococcus aureus growth (MIC, 25 micro g/ml). Specifically, under standard room illumination, phloxine B at a concentration of 100 micro g/ml killed 99% of the cultures (mid-log phase). It also reduced S. aureus CFU by 10(4). Structure

2002 Antimicrobial Agents and Chemotherapy

136482. Sequential emergence of antibiotic resistance in enterococcal bloodstream isolates over 25 years. Full Text available with Trip Pro

Sequential emergence of antibiotic resistance in enterococcal bloodstream isolates over 25 years. We determined the antibiotic susceptibilities of 1,785 enterococcal bloodstream isolates collected over 25 years. Antibiotic resistance emerged at a greater rate in Enterococcus faecium than in other enterococcal species, and E. faecium isolates became proportionally more common over time. Our findings confirm the pattern of emerging antibiotic resistance among enterococci and highlight

2002 Antimicrobial Agents and Chemotherapy

136483. Persistent bacteremia in rabbit fetuses despite maternal antibiotic therapy in a novel intrauterine-infection model. Full Text available with Trip Pro

Persistent bacteremia in rabbit fetuses despite maternal antibiotic therapy in a novel intrauterine-infection model. The effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model of Escherichia coli maternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (...) (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, quantitative blood cultures, fetal histology in treated versus untreated groups, and maternal and fetal antibiotic concentrations in plasma in treated animals. Antibiotic therapy led to dramatic improvement in maternal outcome (100% survival versus 100% death in the untreated group in association with maternal septicemia). Fetal survival also improved, with the two-drug combination

2003 Antimicrobial Agents and Chemotherapy

136484. Sensitization of Staphylococcus aureus and Escherichia coli to antibiotics by the sesquiterpenoids nerolidol, farnesol, bisabolol, and apritone. Full Text available with Trip Pro

Sensitization of Staphylococcus aureus and Escherichia coli to antibiotics by the sesquiterpenoids nerolidol, farnesol, bisabolol, and apritone. The sesquiterpenoids nerolidol, farnesol, bisabolol, and apritone were investigated for their abilities to enhance bacterial permeability and susceptibility to exogenous antimicrobial compounds. Initially, it was observed by flow cytometry that these sesquiterpenoids promoted the intracellular accumulation of the membrane-impermeant nucleic acid stain (...) ethidium bromide by live cells of Lactobacillus fermentum, suggesting that enhanced permeability resulted from disruption of the cytoplasmic membrane. The ability of these sesquiterpenoids to increase bacterial susceptibility to a number of clinically important antibiotics was then investigated. In disk diffusion assays, treatment with low concentrations (0.5 to 2 mM) of nerolidol, bisabolol, or apritone enhanced the susceptibility of Staphylococcus aureus to ciprofloxacin, clindamycin, erythromycin

2003 Antimicrobial Agents and Chemotherapy

136485. CesRK, a two-component signal transduction system in Listeria monocytogenes, responds to the presence of cell wall-acting antibiotics and affects beta-lactam resistance. Full Text available with Trip Pro

CesRK, a two-component signal transduction system in Listeria monocytogenes, responds to the presence of cell wall-acting antibiotics and affects beta-lactam resistance. Listeria monocytogenes is a food-borne pathogen that can cause a variety of illnesses ranging from gastroenteritis to life-threatening septicemia. The beta-lactam antibiotic ampicillin remains the drug of choice for the treatment of listeriosis. We have previously identified a response regulator of a putative two-component (...) signal transduction system that plays a role in the virulence and ethanol tolerance of L. monocytogenes. Here we present evidence that the response regulator, CesR, and a histidine protein kinase, CesK, which is encoded by the gene downstream from cesR, are involved in the ability of L. monocytogenes to tolerate ethanol and cell wall-acting antibiotics of the beta-lactam family. Furthermore, CesRK controls the expression of a putative extracellular peptide encoded by the orf2420 gene, located

2003 Antimicrobial Agents and Chemotherapy

136486. Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections. Full Text available with Trip Pro

Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections. Previous studies have shown that there is considerable variation in the methods and media used to determine the susceptibility of Neisseria meningitidis to antimicrobial agents in different countries. In this study, national and regional reference laboratories used a standardized methodology to determine the MICs of antibiotics used (...) supplemented with sheep blood (MH+B), and MH supplemented with heated (chocolated) blood. Several laboratories encountered problems obtaining confluent growth with unsupplemented MH. MH+B was considered to give the most congruent and reproducible results among the study laboratories. The modal MIC for MH+B for each antibiotic and method was calculated to define the MIC consensus, allowing assessment of each individual laboratory's data in relation to the others. The agreement in each antibiotic/method

2003 Antimicrobial Agents and Chemotherapy

136487. Pharmacology of novel heteroaromatic polycycle antibacterials. Full Text available with Trip Pro

Pharmacology of novel heteroaromatic polycycle antibacterials. Heteroaromatic polycycle (HARP) compounds are a novel class of small (M(w), 600 to 650) DNA-binding antibacterials. HARP compounds exhibit a novel mechanism of action by preferentially binding to AT-rich sites commonly found in bacterial promoters and replication origins. Noncovalent binding in the minor groove of DNA results in inhibition of DNA replication and DNA-dependent RNA transcription and subsequent bacterial growth. HARP (...) compounds have previously been shown to have potent in vitro activities against a broad spectrum of gram-positive organisms. The present report describes the extensive profiling of the in vitro and in vivo pharmacology of HARP antibacterials. The efficacies of representative compounds (GSQ-2287, GSQ-10547, and GSQ-11203), which exhibited good MIC activity, were tested in murine lethal peritonitis and neutropenic thigh infection models following intravenous (i.v.) administration. All compounds were

2003 Antimicrobial Agents and Chemotherapy

136488. Effect of parenteral antibiotic administration on establishment of intestinal colonization in mice by Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases. Full Text available with Trip Pro

Effect of parenteral antibiotic administration on establishment of intestinal colonization in mice by Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases. A mouse model was used to test the hypothesis that antibiotics with activity against anaerobes promote overgrowth of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strains in stool. Subcutaneous clindamycin consistently promoted establishment of high-density colonization, whereas piperacillin-tazobactam

2003 Antimicrobial Agents and Chemotherapy

136489. In vivo antibacterial activity of S-3578, a new broad-spectrum cephalosporin: methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa experimental infection models. Full Text available with Trip Pro

In vivo antibacterial activity of S-3578, a new broad-spectrum cephalosporin: methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa experimental infection models. The in vivo antibacterial activity of S-3578, a new parental cephalosporin, was compared with those of cefepime, ceftriaxone, ceftazidime, imipenem-cilastatin, and vancomycin. The efficacy of S-3578 against systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) SR3637 (50% effective dose [ED

2003 Antimicrobial Agents and Chemotherapy

136490. In vitro susceptibilities of seven Leptospira species to traditional and newer antibiotics. Full Text available with Trip Pro

In vitro susceptibilities of seven Leptospira species to traditional and newer antibiotics. Human leptospirosis is generally treated with penicillin or doxycycline. We studied the susceptibilities of 11 serovars (seven species) of Leptospira to 14 antibiotics. With the exception of chloramphenicol, all tested agents were at least as potent as penicillin and doxycycline, with the macrolide and ketolide drugs producing the lowest MICs (and minimal bactericidal concentrations).

2003 Antimicrobial Agents and Chemotherapy

136491. Reduced release of pneumolysin by Streptococcus pneumoniae in vitro and in vivo after treatment with nonbacteriolytic antibiotics in comparison to ceftriaxone. Full Text available with Trip Pro

Reduced release of pneumolysin by Streptococcus pneumoniae in vitro and in vivo after treatment with nonbacteriolytic antibiotics in comparison to ceftriaxone. Pneumolysin, a virulence factor of Streptococcus pneumoniae with cytotoxic and proinflammatory activities, occurs at concentrations from 0.85 to 180 ng/ml in cerebrospinal fluid (CSF) of meningitis patients. In pneumococcal cultures and in a rabbit meningitis model, the concentrations of pneumolysin in supernatant and CSF were lower (...) after addition of nonbacteriolytic bactericidal antibiotics (rifampin and clindamycin) than after incubation with ceftriaxone.

2003 Antimicrobial Agents and Chemotherapy

136492. New plasmid-borne antibiotic resistance gene cluster in Pasteurella multocida. (Abstract)

New plasmid-borne antibiotic resistance gene cluster in Pasteurella multocida. A new antibiotic resistance gene cluster comprising genes for sulfonamide (sul2), streptomycin (strA-strB), and tetracycline [tetR-tet(H)] resistance was detected on plasmid pVM111 from Pasteurella multocida. The tetR-tet(H) gene region was inserted between sul2 and strA, possibly by illegitimate recombination. Two potential recombination sites of 18 and 25 bp were identified.

2003 Antimicrobial Agents and Chemotherapy

136493. Multiple antibiotic resistance gene transfer from animal to human enterococci in the digestive tract of gnotobiotic mice. Full Text available with Trip Pro

Multiple antibiotic resistance gene transfer from animal to human enterococci in the digestive tract of gnotobiotic mice. It has been proposed that food animals represent the source of glycopeptide resistance genes present in enterococci from humans. We demonstrated the transfer of vanA and of other resistance genes from porcine to human Enterococcus faecium at high frequency in the digestive tract of gnotobiotic mice. Tylosin in the drinking water favored colonization by transconjugants.

2003 Antimicrobial Agents and Chemotherapy

136494. Antibiotic-dependent induction of Pseudomonas putida DOT-T1E TtgABC efflux pump is mediated by the drug binding repressor TtgR. Full Text available with Trip Pro

ttgABC and ttgR promoters and dissociates from it in the presence of chloramphenicol and tetracycline. These results suggest that the TtgR repressor is able to bind to structurally different antibiotics, which allows induction of TtgABC multidrug efflux pump expression in response to these antimicrobial agents. This is the first case in which the expression of a drug transporter of the resistance-nodulation-division family has been shown to be regulated directly by antibiotics. (...) Antibiotic-dependent induction of Pseudomonas putida DOT-T1E TtgABC efflux pump is mediated by the drug binding repressor TtgR. Pseudomonas putida is well known for its metabolic capabilities, but recently, it has been shown to exhibit resistance to a wide range of antibiotics. In P. putida DOT-T1E, the TtgABC efflux pump, which has a broad substrate specificity, extrudes antibiotics such as ampicillin, carbenicillin, tetracycline, nalidixic acid, and chloramphenicol. We have analyzed

2003 Antimicrobial Agents and Chemotherapy

136495. In vitro antibacterial potency and spectrum of ABT-492, a new fluoroquinolone. Full Text available with Trip Pro

In vitro antibacterial potency and spectrum of ABT-492, a new fluoroquinolone. ABT-492 demonstrated potent antibacterial activity against most quinolone-susceptible pathogens. The rank order of potency was ABT-492 > trovafloxacin > levofloxacin > ciprofloxacin against quinolone-susceptible staphylococci, streptococci, and enterococci. ABT-492 had activity comparable to those of trovafloxacin, levofloxacin, and ciprofloxacin against seven species of quinolone-susceptible members of the family (...) and antibacterial activity. In particular, ABT-492 was more active than trovafloxacin and levofloxacin against multidrug-resistant Streptococcus pneumoniae, including strains resistant to penicillin and macrolides, and H. influenzae, including beta-lactam-resistant strains. It retained greater in vitro activity than the comparators against S. pneumoniae and H. influenzae strains resistant to other quinolones due to amino acid alterations in the quinolone resistance-determining regions of the target

2003 Antimicrobial Agents and Chemotherapy

136496. Rapid direct method for monitoring antibiotics in a mouse model of bacterial biofilm infection. Full Text available with Trip Pro

Rapid direct method for monitoring antibiotics in a mouse model of bacterial biofilm infection. We have developed a rapid, continuous method for monitoring the effectiveness of several antibacterial agents in real time, noninvasively, by using a recently described mouse model of chronic biofilm infection (J. L. Kadurugamuwa et al., Infect. Immun. 71:882-890, 2003), which relies on biophotonic imaging of bioluminescent bacteria. To facilitate real-time monitoring of infection, we used (...) a Staphylococcus aureus isolate that was made bioluminescent by inserting a modified lux operon into the bacterial chromosome. This bioluminescent reporter bacterium was used to study the antimicrobial effects of several antibiotics belonging to different molecular families. Treatment with rifampin, tobramycin, and ciprofloxacin was started 7 days after subcutaneous implantation of catheters precolonized with 10(4) CFU of S. aureus. Three different doses of antibiotics were administered twice a day for 4

2003 Antimicrobial Agents and Chemotherapy

136497. Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae. Full Text available with Trip Pro

Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae. Community distribution of azithromycin has an important role to play in trachoma control. Previous studies have suggested that this may increase the prevalence of macrolide-resistant Streptococcus pneumoniae. S. pneumoniae was isolated from children under 7 years of age in Rombo District, northern Tanzania, before and 2 and 6 months after community-wide administration

2003 Antimicrobial Agents and Chemotherapy

136498. Helicobacter pylori reinfection is common in Peruvian adults after antibiotic eradication therapy. Full Text available with Trip Pro

Helicobacter pylori reinfection is common in Peruvian adults after antibiotic eradication therapy. To characterize posttreatment recurrence of Helicobacter pylori in Peru, 192 adults with H. pylori-positive gastric biopsy specimens were monitored by (14)C-Urea breath test, after eradication of H. pylori by use of amoxicillin, clarithromycin, and omeprazole. The cumulative risk of recurrence at 18 months was 30.3% (95% confidence interval, 21.4%-39.3%). Randomly amplified polymorphic DNA (...) (adjusted RR, 0.20). Although an increase in the anti-H. pylori IgG antibody titer corresponded to recurrence, pretreatment and recurrent infections were similar with respect to quantitative culture colony counts and histologic characteristics, suggesting that neither prior eradication nor the memory immune response measurably alters the risk or burden of recurrent infection. Although eradication with antibiotics was successful, the high rate of reinfection suggests that treatment is unlikely to have

2003 Journal of Infectious Diseases

136499. Exploiting genomics, genetics and chemistry to combat antibiotic resistance. (Abstract)

Exploiting genomics, genetics and chemistry to combat antibiotic resistance. To address the worsening problem of antibiotic-resistant bacteria there is an urgent need to develop new antibiotics. Comparative genomics and molecular genetics are being applied to produce lists of essential new targets for compound screening programmes. Combinatorial chemistry and structural biology are being applied to rapidly explore and optimize the interactions between lead compounds and their biological targets (...) . Several compounds that have been identified from target-based screens are now in development, but technical and economic constraints might result in a trickle, rather than a flood, of new antibiotics onto the market in the near future.

2003 Nature Reviews. Genetics

136500. Genetic strategies for antibacterial drug discovery. (Abstract)

Genetic strategies for antibacterial drug discovery. The availability of genome sequences is revolutionizing the field of microbiology. Genetic methods are being modified to facilitate rapid analysis at a genome-wide level and are blossoming for human pathogens that were previously considered intractable. This revolution coincided with a growing concern about the emergence of microbial drug resistance, compelling the pharmaceutical industry to search for new antimicrobial agents (...) . The availability of the new technologies, combined with many genetic strategies, has changed the way that researchers approach antibacterial drug discovery.

2003 Nature Reviews. Genetics

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