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PubMed1991

Ofloxacin in lower respiratory tract infections.

In order to determine the efficacy and safety of the new quinolone ofloxacin in the treatment of chronic lower respiratory disease, 674 patients (353 with chronic bronchitis, 212 with community-acquired pneumonia and 109 with hospital-acquired pneumonia) were treated with ofloxacin 200 mg twice a day. In total, 627 patients (93%) showed a satisfactory clinical response, and 47 patients (7%) had no change or deterioration. Neither severe side effects nor interactions between ofloxacin and coadministered theophylline were seen. This is important in patients suffering from chronic obstructive airways disease. The antibiotic spectrum of ofloxacin covers nearly all bacterial pathogens causing infectious respiratory disease; furthermore, ofloxacin reaches high concentrations in pulmonary secretions and tissue. Ofloxacin is a proven antibiotic substance useful in the treatment of lower respiratory tract infections.

Bacterial Infections↗
PubMed2002

Characteristics of clinical Acinetobacter spp. strains.

Resistance to 13 antimicrobial agents, resistance to the bactericidal activity of human serum, hydrophobic properties, lipolytic activity and production of histamine were determined in a total of 50 clinical Acinetobacter spp. strains (A. baumannii, A. lwoffii, A. calcoaceticus, A. haemolyticus). None of the tested isolates showed resistance to meropenem and none of A. lwoffii, A. calcoaceticus and A. haemolyticus strains were resistant to amikacin. Forty-six strains (92%) manifested resistance to ampicillin, 90% to cefuroxime, 68% to ciprofloxacin, 58% to piperacillin, gentamicin and cotrimaxazole, 50% to cefotaxime, 44% to amikacin, 42% to ceftazidime, 38% to piperacillin/tazobactam, 24% to netilmicin and 16% to ampicillin/sulbactam. In particular, A. baumannii and A. calcoaceticus strains showed considerable antibiotic resistance. Thirty-one isolates (62%) showed serum resistance; intermediate sensitivity was found in 19 isolates (38%). The majority of the strains (72%) demonstrated a strongly hydrophobic character; 16% of isolates exhibited moderate hydrophobic properties. All strains showed lipolytic activity; production of histamine was detected in 14 of 43 strains examined.

Acinetobacter↗
PubMed2004

Response of biofilm bacteria to dissolved organic matter from decomposing maple leaves.

Stream bacteria play an important role in the utilization of dissolved organic matter (DOM) leached from leaves, and in transfer of this DOM to other trophic levels. Leaf leachate is a mixture of labile, recalcitrant, and inhibitory compounds, and bacterial communities vary in their ability to utilize leachate. The purpose of this study was to determine the effects of DOM from sugar maple leaves on bacterial populations in biofilms on decomposing leaf surfaces. Populations of Acinetobacter calcoaceticus, Burkholderia cepacia, and Pseudomonas putida were enumerated on decomposing maple leaves in a northeast Ohio stream using fluorescence in situ hybridization. Additionally, artificial substrata consisting of PVC-end caps filled with agar supplemented with leaf leachate and covered with cellulose filters were used to determine bacterial response to leachate from leaves at different stages of decomposition. Population sizes of bacterial species exhibited different responses. Leachate did not affect A. calcoaceticus. B. cepacia was tolerant of phenolic compounds released from leaves and the population size increased when DOM concentrations were greatest. In contrast, P. putida was inhibited by phenolic components of leachate when total DOM concentrations were greatest. Differences in response of the bacterial species to components of leaf leachate indicate the complexity of microbial population dynamics and interactions with DOM. Differences among species in response to DOM have the potential to influence transport and retention of organic matter in stream ecosystems.

Acer↗
PubMed2000

[Epidemiology and therapy of bacterial infections in geriatrics].

As the elderly segment of our population expands, there is an increase of therapeutic problems considering this age group. The elderly patient is generally susceptible to infections because of the decline in host defense mechanisms that occurs with aging, and the underlying chronic diseases of these patients. Increasing numbers of elderly people are being treated in hospitals and are additionally at particular risk of acquiring nosocomial infections with antibiotic-resistant organisms. This article focuses on the epidemiological considerations, risk factors, types of infections that occur in elderly patients, and the guidelines for empiric therapy. The most common infections of the elderly are respiratory tract infection, urinary tract infection, and skin and soft tissue infection. Empirical therapy should be broader in spectrum for elderly patients since the variety of infecting bacteria tends to be greater and the choice of antimicrobial therapy must be based on risk stratification (age, medical illnesses, and severity of presentation). Many additional aspects, e.g., route of administration, drug pharmacokinetics and pharmacodynamics, drug toxicity and drug-drug interactions, compliance, and multiple underlying diseases (e.g., renal failure) must be considered in the rational selection of antibiotic regimen.

Aged↗
PubMed1987

The immune response to dietary antigens and its influence on disease susceptibility in farm animals.

Transient hypersensitivity reactions of the intestinal immune system to dietary antigens result in increases in enterocyte turnover and villous atrophy. These changes occur in the intestine of the post weaned piglet and precede the proliferation of E. coli and the development of post-weaning diarrhea. We therefore postulated that a transient cell mediated immune response to dietary antigens may increase susceptibility to disease. The interaction of dietary and microbial antigens upon the gut immune system has been investigated in mice and pigs and it has been shown that both exert powerful regulatory effects upon each other.

Adjuvants, Immunologic↗
PubMedDate not supplied

Pharmacodynamic (kinetic) considerations in the treatment of moderately severe infections with cefotaxime.

Information about the pharmacodynamics of beta-lactams has accumulated rapidly over the last 20 years, and their application to cefotaxime are discussed in this review. Application of pharmacodynamics requires an integration of the pharmacokinetic and in vitro properties of the agent. Cefotaxime is similar to other beta-lactams in that it has little concentration-dependent killing and produces no postantibiotic effect against Gram-negative bacteria. However, it has a microbiologically active metabolite, deascetylcefotaxime, which can show synergy, partial synergy, or an additive effect in combination with the parent drug. More than any other technique, animal models have been able to elucidate the pharmacokinetic parameters that predict efficacy in vivo. They have shown that for beta-lactams it is the time that levels exceed the minimum inhibitory concentration (MIC) that is the most important determinant of efficacy. For bacteria to have no postantibiotic effect, plasma levels need to exceed the MIC for the whole of the dosing interval to achieve maximum killing at the site of infection. When applying these concepts as the most stringent criteria for efficacy using pharmacokinetic values from young, healthy volunteers, it can be shown that organisms with MICs of < or = 0.03 microgram/ml for a 1-g dose and 0.06 microgram/ml for a 2-g dose to achieve optimum efficacy with 12-h dosing of cefotaxime. However, two clinical studies have demonstrated trough levels much greater than would be predicted from these pharmacokinetic values, as a result of the effects of decreased renal function accompanying sepsis and older age. These studies showed that organisms with MICs < or = 1 microgram/ml for a 1-g dose or 2 micrograms/ml for a 2-g 12-h dose were covered for the whole of the dosing interval. Thus, all strains of Enterobacteriaceae and pathogenic Neisseria spp. that lack resistance mechanisms to third-generation cephalosporins would be covered using 12-h dosing schedules.

Animals↗
PubMed1994

Chloroquine does not enhance the activity of clarithromycin against multiplication of Mycobacterium avium within human macrophages.

SETTING: Chloroquine, an alkalinizing lysosomotropic agent, enhances the intracellular activity of antibiotics against Mycobacterium tuberculosis or Coxiella burnetii. OBJECTIVE: To determine if chloroquine modifies the activity of clarithromycin, less effective at acidic pH, against intracellular Mycobacterium avium. DESIGN: The activity of clarithromycin (4 micrograms/ml) against the MO-1 strain of M. avium was evaluated within human macrophages in presence of chloroquine (5 micrograms/ml). The minimal inhibitory concentration of clarithromycin for the strain was 2 micrograms/ml. RESULTS: While clarithromycin alone did decrease the intracellular infection at day 7 of culture (P < 0.01), chloroquine alone did not impede the intracellular growth of M. avium, and did not enhance the activity of clarithromycin. CONCLUSION: Chloroquine should not improve clarithromycin treatment against M. avium infection.

Cells, Cultured↗
PubMed2005

Design and synthesis of macrocycles active against vancomycin-resistant enterococci (VRE): the interplay between d-Ala-d-Lac binding and hydrophobic effect.

A modified vancomycin binding pocket (D-O-E ring) incorporating a CHNHCOR function at the AA4 position is designed and synthesized. Potent bioactivities against both sensitive- and resistant-strain are found for some of these compounds (MIC 4 microg/mL against VREF). From this preliminary SAR studies, it was speculated that the D-Ala-D-Ala binding was required for this series of compounds since the corresponding des-leucine derivative is inactive. The presence of long aliphatic chain was important for the desired activities and such hydrophobic effect is specific as no beneficial effect is observed when the same aliphatic chain was attached to the other part of the molecule.

Anti-Bacterial Agents↗
PubMed2005

Levels of complexity in pathogen recognition by C-type lectins.

In pathogen recognition by C-type lectins, several levels of complexity can be distinguished; these might modulate the immune response in different ways. Firstly, the pathogen-associated molecular pattern repertoire expressed at the microbial surface determines the interactions with specific receptors. Secondly, each immune cell type possesses a specific set of pathogen-recognition receptors. Thirdly, changes in the cell-surface distribution of C-type lectins regulate carbohydrate binding by modulating receptor affinity for different ligands. Crosstalk between these receptors results in a network of multimolecular complexes, adding a further level of complexity in pathogen recognition.

Animals↗
PubMed2024

metaExpertPro: A Computational Workflow for Metaproteomics Spectral Library Construction and Data-Independent Acquisition Mass Spectrometry Data Analysis.

Analysis of large-scale data-independent acquisition mass spectrometry metaproteomics data remains a computational challenge. Here, we present a computational pipeline called metaExpertPro for metaproteomics data analysis. This pipeline encompasses spectral library generation using data-dependent acquisition MS, protein identification and quantification using data-independent acquisition mass spectrometry, functional and taxonomic annotation, as well as quantitative matrix generation for both microbiota and hosts. By integrating FragPipe and DIA-NN, metaExpertPro offers compatibility with both Orbitrap and timsTOF MS instruments. To evaluate the depth and accuracy of identification and quantification, we conducted extensive assessments using human fecal samples and benchmark tests. Performance tests conducted on human fecal samples indicated that metaExpertPro quantified an average of 45,000 peptides in a 60-min diaPASEF injection. Notably, metaExpertPro outperformed three existing software tools by characterizing a higher number of peptides and proteins. Importantly, metaExpertPro maintained a low factual false discovery rate of approximately 5% for protein groups across four benchmark tests. Applying a filter of five peptides per genus, metaExpertPro achieved relatively high accuracy (F-score&#xa0;=&#xa0;0.67-0.90) in genus diversity and showed a high correlation (rSpearman&#xa0;=&#xa0;0.73-0.82) between the measured and true genus relative abundance in benchmark tests. Additionally, the quantitative results at the protein, taxonomy, and function levels exhibited high reproducibility and consistency across the commonly adopted public human gut microbial protein databases IGC and UHGP. In a metaproteomic analysis of dyslipidemia patients, metaExpertPro revealed characteristic alterations in microbial functions and potential interactions between the microbiota and the host.

Proteomics↗
PubMed2003

Individual substitution analogs of Mel(12-26), melittin's C-terminal 15-residue peptide: their antimicrobial and hemolytic actions.

Residues 1-9 of M(12-26) (GLPALISWIKRKRQQ-NH2), the C-terminal 15-residue segment of melittin, were substituted individually to change the hydropathicities in these positions. Antimicrobial and hemolytic activities of these peptides were determined. The results showed increased antimicrobial activities with increased hydrophobicities at almost all the positions studied. The effects at positions 2, 5, 8 and 9 were significant while the effects at the other positions were small. These two groups of residues were located on the opposite faces of the alpha-helix. In other words, the hydrophobicities of the two faces were favorable, but one face (the more favorable face) contributed more to the antimicrobial activities than the other (the less favorable face). The hydrophobicity, not the amphipathicity, seems to be crucial for antimicrobial activity. In contrast, the hydrophobicity of one face was favorable but the other was unfavorable for the hemolytic activity, indicating that the amphipathicity may be important for hemolysis. Interestingly, the more favorable face for antimicrobial activity was located opposite to the favorable face for hemolytic activity, indicating the direction of the hydrophobic face for the antimicrobial activity and direction of the amphipathicity for the hemolytic activity were also important.

Amino Acid Sequence↗
PubMed1995

Quinolones.

Fluoroquinolones represent a major advance in antimicrobial chemotherapy. Currently, there are five fluoroquinolones approved by the FDA, and many more quinolones are expected to become available in years to come. Although their clinical utility is constantly expanding, they have been best studied in complicated urinary tract infections, chronic osteomyelitis caused by gram-negative bacilli, bacterial gastrointestinal infections such as traveler's diarrhea and typhoid fever, and uncomplicated gonococcal infections and in the prophylaxis of bacterial infections in patients with neutropenia. These agents have the convenience of oral administration, favorable pharmacokinetic properties, and low toxicity profiles but should be used advisedly because indiscriminate use may result in the early emergence of resistance.

4-Quinolones↗
PubMed1999

PGG-glucan, a soluble beta-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-kappa B-like factor in human PMN: evidence for a glycosphingolipid beta-(1,3)-glucan receptor.

PGG-Glucan, a soluble beta-(1,6)-branched beta-(1,3)-linked glucose homopolymer derived from the cell wall of the yeast Saccharomyces cerevisiae, is an immunomodulator which enhances leukocyte anti-infective activity and enhances myeloid and megakaryocyte progenitor proliferation. Incubation of human whole blood with PGG-Glucan significantly enhanced the oxidative burst response of subsequently isolated blood leukocytes to both soluble and particulate activators in a dose-dependent manner, and increased leukocyte microbicidal activity. No evidence for inflammatory cytokine production was obtained under these conditions. Electrophoretic mobility shift assays demonstrated that PGG-Glucan induced the activation of an NF-kappaB-like nuclear transcription factor in purified human neutrophils. The binding of 3H-PGG-Glucan to human leukocyte membranes was specific, concentration-dependent, saturable, and high affinity (Kd approximately 6 nM). A monoclonal antibody specific to the glycosphingolipid lactosylceramide was able to inhibit activation of the NF-kappaB-like factor by PGG-Glucan, and ligand binding data, including polysaccharide specificity, suggested that the PGG-Glucan binding moiety was lactosylceramide. These results indicate that PGG-Glucan enhances neutrophil anti-microbial functions and that interaction between this beta-glucan and human neutrophils is mediated by the glycosphingolipid lactosylceramide present at the cell surface.

Adjuvants, Immunologic↗
PubMed2000

Accurate diagnosis of Helicobacter pylori. Culture, including transport.

Bacteriology laboratories are interested in culturing H. pylori for several reasons: (1) to investigate its growth requirements and metabolism; (2) for diagnostic purposes; (3) to establish the antibiotic susceptibility of isolates; (4) to identify potential virulence factors; and (5) to investigate microbial host-cell interactions. Despite the reasons listed, culture of H. pylori from gastric biopsy specimens is becoming less popular among clinical laboratories and physicians. The main reason is that it has become generally accepted that culture techniques are too demanding with many factors that must be controlled, in addition to simple and less expensive methods now available. Some of the disadvantages of culture include (1) special conditions for specimen transportation, (2) speed in processing of the sample to increase the probability of recovering the organism, (3) the use of expensive and complicated media with special conditions for maintenance, (4) the need for special incubation conditions, and (5) the length of time necessary to obtain a result for establishing treatment options in the patient. This article reviews aspects of H. pylori culture that could explain use being relegated to only a few clinical laboratories, some regional laboratories, and reference centers. There are several misconceptions in relation to culture techniques, such as transport and the processing of biopsy specimens. This article has mentioned simple and clear points that optimize the recovery rates of H. pylori by culture.

Bacteriological Techniques↗
PubMed2001

In vitro activity of KRM-1648, either singly or in combination with ofloxacin, against Mycobacterium ulcerans.

The antimicrobial effect of a benzoxazinorifamycin, KRM-1648, either alone or in combination with ofloxacin, was evaluated in vitro against two type strains and six clinical isolates of Mycobacterium ulcerans. Growth of M. ulcerans was measured by plate counts and the BACTEC radiometric method. The minimal inhibitory concentration as well as minimal bactericidal concentration of KRM-1648 against M. ulcerans was between 0.012 and 0.025 mg/l, while corresponding values for rifampicin and rifabutin were in the range of 0.1-0.8 mg/l and 0.1-0.4 mg/l respectively. When combined with ofloxacin, KRM-1648 exhibited strong synergistic activity while only additive effects were observed with the combination of rifampicin (or rifabutin) and ofloxacin. These results suggest that KRM-1648 has a great potential in the treatment of M. ulcerans infection.

Anti-Infective Agents↗
PubMed1999

Bactericidal action of ampicillin/sulbactam against intracellular mycobacteria.

The resistance of mycobacteria to beta-lactam antibiotics is attributed to their ability to synthesize beta-lactamase. In our previous studies, beta-lactam/beta-lactamase-inhibitor combinations suppressed the growth of several mycobacteria in axenic cultures and ampicillin/sulbactam was bactericidal to Mycobacterium tuberculosis H37Rv in vitro, and to Mycobacterium leprae multiplying in mouse foot-pads. Since both these organisms multiply in phagocytic cells in the host, it is important to know whether the drug combination is active against mycobacteria multiplying in macrophages. We tested the action of ampicillin/sulbactam against four potentially pathogenic (to humans or to animals) mycobacteria, M. simiae, M. haemophilum, M. avium, M. microti, when phagocytosed by mouse macrophages. Bacteria were exposed to monolayers of peritoneal macrophages harvested from BALB/c mice. Unphagocytosed bacilli were removed and three concentrations of ampicillin/sulbactam were tested. Optimum activity was observed at 100 mg/l which killed 58-97% of the mycobacteria within macrophages, as determined by the CFU. beta-Lactam/beta-lactamase-inhibitors, especially ampicillin/sulbactam, might provide an effective alternative therapy against infections caused by mycobacteria resistant to other drugs.

Ampicillin↗
PubMed2001

Innate immunity in plants.

Studies of receptors and signal-transduction components that play a role in plant disease resistance have revealed remarkable similarities with innate immunity pathways in insects and mammals. In plants, specific receptors encoded by disease-resistance genes interact with products of microbial effector genes to activate defence responses. Resistance proteins have been found to have motifs in common with components of immune response pathways in mammals and invertebrates, and to rely on similar downstream signalling components. In the future, the sharing of ideas among plant and animal biologists is likely to broaden our understanding of defence responses in diverse organisms.

Animals↗