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136541. Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: in vitro kinetic model. Full Text available with Trip Pro

Suboptimal antibiotic dosage as a risk factor for selection of penicillin-resistant Streptococcus pneumoniae: in vitro kinetic model. Optimizing pharmacokinetic/pharmacodynamic indices of antibiotics to obtain clinical and microbiological efficacy is essential, but dosing regimens must also be tailored to minimize the risk for emergence of resistance. The aim of the present study was to investigate whether certain concentrations of benzylpenicillin are critical for the selection of resistant (...) antibiotic-containing plates. The T>MIC varied from 46 to 100% for the susceptible strain, from 6 to 100% for the intermediate strain, and from 0 to 48% for the resistant strain. Our study, which may mimic the clinical situation with carriage of a mixed population of S. pneumoniae with different antibiotic susceptibilities, has shown that selection of resistant bacteria may easily occur if dosing regimens are only targeted toward fully susceptible strains.

2003 Antimicrobial Agents and Chemotherapy

136542. Culture and antibiotic susceptibility of Bartonella quintana in human erythrocytes. Full Text available with Trip Pro

Culture and antibiotic susceptibility of Bartonella quintana in human erythrocytes. Bartonella quintana, the agent of trench fever, has recently been implicated in various diseases, in particular, bacteremia and endocarditis in homeless people. The host cell of Bartonella spp. is believed to be the erythrocyte, and in the present study we demonstrate that B. quintana can be cultured in vitro in human erythrocytes. The bacteria were found to be intraerythrocytic by laser confocal microscopy (...) with Bartonella species-specific monoclonal antibodies. Infections with B. quintana decreased the life span of erythrocytes in culture from 8.6 to 4.8 days. In the culture system we found that most of the antibiotics that we tested (doxycycline, fluoroquinolone compounds, and beta-lactams) were not bactericidal. Gentamicin was bactericidal at 4 micro g/ml, as was rifampin, but to a lesser extent. At this concentration, gentamicin has been shown to enter erythrocytes slowly and to reach a peak level of 0.26

2003 Antimicrobial Agents and Chemotherapy

136543. Inhibition of secretion of interleukin-1alpha and tumor necrosis factor alpha by the ketolide antibiotic telithromycin. Full Text available with Trip Pro

Inhibition of secretion of interleukin-1alpha and tumor necrosis factor alpha by the ketolide antibiotic telithromycin. The antibiotic telithromycin was examined for its effect on secretion of interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated monocytes of eight human donors. Secretion of each cytokine was significantly increased by LPS alone, whereas treatment with telithromycin significantly inhibited

2002 Antimicrobial Agents and Chemotherapy

136544. Mycothiol-deficient Mycobacterium smegmatis mutants are hypersensitive to alkylating agents, free radicals, and antibiotics. Full Text available with Trip Pro

Mycothiol-deficient Mycobacterium smegmatis mutants are hypersensitive to alkylating agents, free radicals, and antibiotics. Mycothiol (MSH; 1D-myo-inosityl 2-[N-acetyl-L-cysteinyl]amido-2-deoxy-alpha-D-glucopyranoside) is the major low-molecular-weight thiol produced by mycobacteria. Mutants of Mycobacterium smegmatis mc(2)155 deficient in MSH production were produced by chemical mutagenesis as well as by transposon mutagenesis. One chemical mutant (mutant I64) and two transposon mutants (...) -glucopyranoside ligase (MshC) activities of the three mutant strains were < or =2% that of the parent strain. Phenotypic analysis revealed that these MSH-deficient mutants possess increased susceptibilities to free radicals and alkylating agents and to a wide range of antibiotics including erythromycin, azithromycin, vancomycin, penicillin G, rifamycin, and rifampin. Conversely, the mutants possess at least 200-fold higher levels of resistance to isoniazid than the wild type. We mapped the mutation

2002 Antimicrobial Agents and Chemotherapy

136545. Determination of antibiotic effect in an in vitro pharmacodynamic model: comparison with an established animal model of infection. Full Text available with Trip Pro

Determination of antibiotic effect in an in vitro pharmacodynamic model: comparison with an established animal model of infection. Animal infection models have historically been used to study pharmacodynamic relationships. Similar results could theoretically be produced by using an in vitro pharmacodynamic model as an alternative to animal models. We compared the antibiotic effects of ticarcillin administered in various doses and dosing regimens against Pseudomonas aeruginosa ATCC 27853 under

2002 Antimicrobial Agents and Chemotherapy

136546. Staphylococcus sciuri gene erm(33), encoding inducible resistance to macrolides, lincosamides, and streptogramin B antibiotics, is a product of recombination between erm(C) and erm(A). Full Text available with Trip Pro

Staphylococcus sciuri gene erm(33), encoding inducible resistance to macrolides, lincosamides, and streptogramin B antibiotics, is a product of recombination between erm(C) and erm(A). A gene which mediates inducible resistance to macrolides, lincosamides, and streptogramin B antibiotics, designated erm(33), was detected on the Staphylococcus sciuri plasmid pSCFS1. Analysis of the erm(33) reading frame suggested that this gene was the product of a recombination between an erm(C) gene and an erm

2002 Antimicrobial Agents and Chemotherapy

136547. Worldwide antimicrobial susceptibility patterns and pharmacodynamic comparisons of gatifloxacin and levofloxacin against Streptococcus pneumoniae: report from the Antimicrobial Resistance Rate Epidemiology Study Team. Full Text available with Trip Pro

Worldwide antimicrobial susceptibility patterns and pharmacodynamic comparisons of gatifloxacin and levofloxacin against Streptococcus pneumoniae: report from the Antimicrobial Resistance Rate Epidemiology Study Team. The use of fluoroquinolones for the treatment of community-acquired respiratory tract infection is increasing. Since for Streptococcus pneumoniae a ratio of the 24-h area under the concentration-time curve (AUC(24)) for the agent to the MIC (AUC(24)/MIC) greater than 30 (...) for the fraction of unbound drug (f(u)) is the major pharmacokinetic-pharmacodynamic (PK-PD) parameter correlating with bacterial eradication by fluoroquinolones in nonclinical models of infection and in infected patients, the Antimicrobial Resistance Rate Epidemiology Study Team systematically compared the in vitro susceptibility patterns and estimated the probability of attainment of the PK-PD target ratios for gatifloxacin and levofloxacin against pneumococci worldwide. Monte Carlo simulation was used

2003 Antimicrobial Agents and Chemotherapy

136548. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Full Text available with Trip Pro

Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. The roles of slow antibiotic penetration, oxygen limitation, and low metabolic activity in the tolerance of Pseudomonas aeruginosa in biofilms to killing by antibiotics were investigated in vitro. Tobramycin and ciprofloxacin penetrated biofilms but failed to effectively kill the bacteria. Bacteria in colony biofilms survived (...) prolonged exposure to either 10 micro g of tobramycin ml(-1)or 1.0 micro g of ciprofloxacin ml(-1). After 100 h of antibiotic treatment, during which the colony biofilms were transferred to fresh antibiotic-containing plates every 24 h, the log reduction in viable cell numbers was only 0.49 +/- 0.18 for tobramycin and 1.42 +/- 0.03 for ciprofloxacin. Antibiotic permeation through colony biofilms, indicated by a diffusion cell bioassay, demonstrated that there was no acceleration in bacterial killing

2003 Antimicrobial Agents and Chemotherapy

136549. Discovery of a novel and potent class of FabI-directed antibacterial agents. Full Text available with Trip Pro

, which depend on FabK and both FabK and FabI, respectively, for their enoyl-ACP reductase function. These results show that compound 4 is representative of a new, totally synthetic series of antibacterial agents that has the potential to provide novel alternatives for the treatment of S. aureus infections that are resistant to our present armory of antibiotics. (...) Discovery of a novel and potent class of FabI-directed antibacterial agents. Bacterial enoyl-acyl carrier protein (ACP) reductase (FabI) catalyzes the final step in each elongation cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antibacterial agents. High-throughput screening of the Staphylococcus aureus FabI enzyme identified a novel, weak inhibitor with no detectable antibacterial activity against S. aureus. Iterative medicinal chemistry and X

2002 Antimicrobial Agents and Chemotherapy

136550. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. Full Text available with Trip Pro

Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. Xenodiagnosis by ticks was used to determine whether spirochetes persist in mice after 1 month of antibiotic therapy for vectorborne Borrelia burgdorferi infection. Immunofluorescence and polymerase chain reaction (PCR) were used to show that spirochetes could be found in Ixodes scapularis ticks feeding on 4 of 10 antibiotic-treated mice up to 3 months after therapy (...) . These spirochetes could not be transmitted to naive mice, and some lacked genes on plasmids correlating with infectivity. By 6 months, antibiotic-treated mice no longer tested positive by xenodiagnosis, and cortisone immunosuppression did not alter this result. Nine months after treatment, low levels of spirochete DNA could be detected by real-time PCR in a subset of antibiotic-treated mice. In contrast to sham-treated mice, antibiotic-treated mice did not have culture or histopathologic evidence of persistent

2002 Journal of Infectious Diseases

136551. Evaluation of antibiotic susceptibilities of three rickettsial species including Rickettsia felis by a quantitative PCR DNA assay. Full Text available with Trip Pro

Evaluation of antibiotic susceptibilities of three rickettsial species including Rickettsia felis by a quantitative PCR DNA assay. Rickettsiae grow only intracellularly, and the antibiotic susceptibilities of these bacteria have been assessed by either plaque, dye uptake, or immunofluorescence assays, which are time-consuming. We used a quantitative PCR (with the LightCycler instrument) to assess the levels of inhibition of Rickettisa felis, R. conorii, and R. typhi DNA synthesis (...) in the presence of various antibiotics. We established the kinetics of rickettsial DNA during growth and showed that R. conorii grows more quickly than R. typhi in cell culture, with maximum replication occurring after 5 and 7 days, respectively. The MICs of the antibiotics tested for R. conorii and R. typhi by the quantitative PCR assay were similar to those previously obtained by plaque and dye uptake assays. We found that R. felis is susceptible to doxycycline, rifampin, thiamphenicol, and fluoroquinolones

2002 Antimicrobial Agents and Chemotherapy

136552. N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity. Full Text available with Trip Pro

N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity. Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P(1)' site. Using a combination of iterative parallel synthesis and traditional (...) to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.

2002 Antimicrobial Agents and Chemotherapy

136553. Antibiotic use in Hispanic households, New York city. Full Text available with Trip Pro

Antibiotic use in Hispanic households, New York city. Trained interviewers visited 631 inner city households to determine community prevalence and predictors of antibiotic use. Infectious disease symptoms were reported in 911 (33.2%) of 2,743 household members in the previous 30 days: medical attention was sought by 441 (48.4%) of 911 persons, and 354 (8.9%) of 911 took antibiotics for symptoms. Reported symptoms were respiratory (68.9%(, gastrointestinal (15.3%(, fever (12.8%(, and skin (...) infection (2.8%(. Medical attention was sought significantly more often among those with chronic illness, those born in the United States, and those with fever, runny nose, or skin infections (all p<0.05). Antibiotics were taken significantly more often among those with poor health, those who spent more time at home, and those with fever and respiratory symptoms. Interventions to promote judicious use of antibiotics must include clinicians and the public, and for the Hispanic population

2003 Emerging Infectious Diseases

136554. Consumer attitudes and use of antibiotics. Full Text available with Trip Pro

Consumer attitudes and use of antibiotics. Recent antibiotic use is a risk factor for infection or colonization with resistant bacterial pathogens. Demand for antibiotics can be affected by consumers' knowledge, attitudes, and practices. In 1998-1999, the Foodborne Diseases Active Surveillance Network (FoodNet( conducted a population-based, random-digit dialing telephone survey, including questions regarding respondents' knowledge, attitudes, and practices of antibiotic use. Twelve percent had (...) recently taken antibiotics; 27% believed that taking antibiotics when they had a cold made them better more quickly, 32% believed that taking antibiotics when they had a cold prevented more serious illness, and 48% expected a prescription for antibiotics when they were ill enough from a cold to seek medical attention. These misguided beliefs and expectations were associated with a lack of awareness of the dangers of antibiotic use; 58% of patients were not aware of the possible health dangers. National

2003 Emerging Infectious Diseases

136555. Proteomic approach to understanding antibiotic action. (Abstract)

Proteomic approach to understanding antibiotic action. We have used proteomic technology to elucidate the complex cellular responses of Bacillus subtilis to antimicrobial compounds belonging to classical and emerging antibiotic classes. We established on two-dimensional gels a comprehensive database of cytoplasmic proteins with pIs covering a range of 4 to 7 that were synthesized during treatment with antibiotics or agents known to cause generalized cell damage. Although each antibiotic showed (...) an individual protein expression profile, overlaps in the expression of marker proteins reflected similarities in molecular drug mechanisms, suggesting that novel compounds with unknown mechanisms of action may be classified. Indeed, one such substance, a structurally novel protein synthesis inhibitor (BAY 50-2369), could be classified as a peptidyltransferase inhibitor. These results suggest that this technique gives new insights into the bacterial response toward classical antibiotics and hints at modes

2003 Antimicrobial Agents and Chemotherapy

136556. Transcriptional induction of the penicillin-binding protein 2 gene in Staphylococcus aureus by cell wall-active antibiotics oxacillin and vancomycin. Full Text available with Trip Pro

Transcriptional induction of the penicillin-binding protein 2 gene in Staphylococcus aureus by cell wall-active antibiotics oxacillin and vancomycin. We found an increased abundance of pbpB-specific transcripts in vancomycin intermediate-resistant Staphylococcus aureus (VISA) isolates compared with that found in paired, genetically identical, susceptible isolates. This difference in expression cannot be explained by differences in the pbpB promoter sequence. Since the factors controlling pbpB (...) expression or transcriptional induction of pbpB by vancomycin or oxacillin. Also, MecI, MecR1, BlaI, and BlaR1, regulatory proteins that mediate beta-lactam-inducible expression of mecA and beta-lactamase, were not required for antibiotic induction of pbpB transcription. These data support the idea that pbpB expression is modulated by a trans-acting factor in response to the presence of the cell wall-active antibiotics vancomycin and oxacillin.

2003 Antimicrobial Agents and Chemotherapy

136557. Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics. Full Text available with Trip Pro

Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics. Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino (...) . The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

2003 Antimicrobial Agents and Chemotherapy

136558. Molecular evaluation of antibiotic susceptibility: Tropheryma whipplei paradigm. Full Text available with Trip Pro

Molecular evaluation of antibiotic susceptibility: Tropheryma whipplei paradigm. Tropheryma whipplei, the agent of Whipple's disease, grows fastidiously only in cell cultures without plaque production, and only three strains have been passaged. The formation of bacterial clumps in the supernatant precludes enumeration of viable bacteria and MIC determination. We evaluated the bacteriostatic effects of fluoroquinolones against two T. whipplei isolates by measuring the inhibition of the DNA copy

2003 Antimicrobial Agents and Chemotherapy

136559. Wolbachia pipientis growth kinetics and susceptibilities to 13 antibiotics determined by immunofluorescence staining and real-time PCR. Full Text available with Trip Pro

Wolbachia pipientis growth kinetics and susceptibilities to 13 antibiotics determined by immunofluorescence staining and real-time PCR. Wolbachia spp. are strict intracellular bacteria that infect a wide range of arthropods and filarial nematodes. Filarial nematodes are important causes of human diseases. There is increasing evidence that Wolbachia spp. influence important functions in the biology of the hosts, specifically, infertility. Preliminary experiments with humans and animals have (...) suggested that antibiotics with activity against Wolbachia may help to treat filariasis. In this study, we determined using a real-time quantitative PCR assay the growth kinetics of a strain of Wolbachia pipientis from a mosquito grown in Aa23 cells. The doubling time was estimated to be 14 h. We then determined the susceptibilities of this strain to 13 antibiotics by two methods: an immunofluorescent-antibody test and a real-time quantitative PCR assay. Both techniques gave similar results. Doxycycline

2003 Antimicrobial Agents and Chemotherapy

136560. In vivo antibacterial activity of RWJ-54428, a new cephalosporin with activity against gram-positive bacteria. Full Text available with Trip Pro

In vivo antibacterial activity of RWJ-54428, a new cephalosporin with activity against gram-positive bacteria. RWJ-54428 (MC-02,479) is a new cephalosporin with activity against resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. The in vivo efficacy of RWJ-54428 was evaluated against gram-positive bacteria in four mouse models of infection. RWJ-54428 was effective in vivo

2003 Antimicrobial Agents and Chemotherapy

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