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PubMed2002

Infective endocarditis caused by unusual gram-positive pathogens.

Of a total of 81 patients hospitalized in the infectious diseases department in 1990-2000 with infectious endocarditis caused by Gram-positive pathogen, unusual etiological agents were found in several cases: Streptococcus pyogenes, Streptococcus pneumoniae, Corynebacterium diphtheriae, and Gemella morbillorum. Cardiac defects were present in the latter two patients: bicuspid aortic valve and tetralogy of Fallot. Two patients were successfully treated with antibiotics only and one patient with antibiotics and surgery. The patient with C. diphtheriae endocarditis died due to progressive sepsis and multiple organ failure.

Adult↗

PubMed2006

Study of upper respiratory tract bacterial flora: first report. Variations in upper respiratory tract bacterial flora in patients with acute upper respiratory tract infection and healthy subjects and variations by subject age.

With the appearance of penicillin-resistant Streptococcus pneumoniae, there has been increasing debate concerning antimicrobial treatments for acute upper respiratory tract infection (AURTI) and acute otitis media in children. This study compares the nasopharyngeal bacterial flora in patients with AURTI (AURTI group; 710 subjects) and healthy subjects (HS group; 380 subjects). The comparisons were made between subjects aged 6 years or younger (0-6 subgroup: 330 subjects), between 7 and 74 years (7-74 subgroup: 668 subjects), and 75 years and older (92 subjects), because the subjects were subgrouped as described above dependent on the maturity of the protective immunity. In the HS group 7-74 subgroup, viridans group streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium sp. with a detection rate of 10% or more were classified as normal nasal flora (NNF), and Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were classified as drum cavity pathogens (DCP). In the 0-6 subgroup, although the detection rate for DCP bacteria in the AURTI group tended to be high, it did not reach a significant difference, whereas the detection rate for NNF bacteria was significantly lower. This trend was also observed to some degree in the other age subgroup. In the 0-6 subgroup, leukocyte infiltration observed with a microscope indicated the closest relationship between S. pneumoniae detection rate and detection quantity. These results suggest that in the 0-6 subgroup the tendency for patients with AURTI to have NNF bacteria as well as DCP bacteria should be taken into consideration.

Acute Disease↗

PubMed2006

Coenzyme Q10 production in recombinant Escherichia coli strains engineered with a heterologous decaprenyl diphosphate synthase gene and foreign mevalonate pathway.

In the present work, Escherichia coli DH5alpha was metabolically engineered for CoQ(10) production by the introduction of decaprenyl diphosphate synthase gene (ddsA) from Agrobacterium tumefaciens. Grown in 2YTG medium (1.6% tryptone, 1% yeast extract, 0.5% NaCl, and 0.5% glycerol) with an initial pH of 7, the recombinant E. coli was capable of CoQ(10) production up to 470 microg/gDCW (dry cell weight). This value could be further elevated to 900 microg/gDCW simply by increasing the initial culture pH from 7 to 9. Supplementation of 4-hydroxy benzoate did not improve the productivity any further. However, engineering of a lower mevalonate semi-pathway so as to increase the isopentenyl diphosphate (IPP) supply of the recombinant strain using exogenous mevalonate efficiently increased the CoQ(10) production. Lower mevalonate semi-pathways of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, and Saccharomyces cerevisiae were tested. Among these, the pathway of Streptococcus pneumoniae proved to be superior, yielding CoQ(10) production of 2,700+/-115 microg/gDCW when supplemented with exogenous mevalonate of 3 mM. In order to construct a complete mevalonate pathway, the upper semi-pathway of the same bacterium, Streptococcus pneumoniae, was recruited. In a recombinant E. coli DH5alpha harboring three plasmids encoding for upper and lower mevalonate semi-pathways as well as DdsA enzyme, the heterologous mevalonate pathway could convert endogenous acetyl-CoA to IPP, resulting in CoQ(10) production of up to 2,428+/-75 microg/gDCW, without mevalonate supplementation. In contrast, a whole mevalonate pathway constructed in a single operon was found to be less efficient. However, it provided CoQ(10) production of up to 1,706+/-86 microg/gDCW, which was roughly 1.9 times higher than that obtained by ddsA alone.

Alkyl and Aryl Transferases↗

PubMed2003

Microbiology and management of acute suppurative thyroiditis in children.

This review describes the microbiology, diagnosis and management of suppurative thyroiditis (ST). Staphylococcus aureus, Streptococcus pyogenes, Streptococcus epidermidis, and Streptococcus pneumoniae, are the predominant aerobic isolates. The most common anaerobic bacteria are Gram-negative bacilli and Peptostreptococcus spp. Agents that are rarely recovered include Klebsiella spp., Haemophilus influenzae, Streptococcus viridans, Salmonella spp., Enterobacteriaceae, Mycobacterium tuberculosis, atypical mycobacteria, Aspergillus spp., Coccidioides immitis, Candida spp., Treponema pallidum, and Echinococcus spp. Viruses have been associated with subacute thyroiditis, and include measles, mumps, influenza, enterovirus Epstein-barr, adenovirus, echovirus, and St Louis encephalitis. Therapy includes administration of antibiotics effective against the causative pathogen(s). Proper selection of therapy can be guided by culture of the lesion. Surgical drainage may be necessary in case of suppuration.

Anti-Bacterial Agents↗

PubMed1997

Kinetics of specific salivary IgA responses in man after oral challenge by ribosomal immunostimulant.

The kinetics of specific IgA mucosal responses was assessed in 12 healthy volunteers over 3 weeks of treatment by oral administration of an immunostimulant, Ribomunyl, composed of ribosomes from the four bacteria Streptococcus pyogenes, Streptococcus pneumoniae, Klebsiella pneumoniae and Haemophilus influenzae. The levels of IgA specific for these four bacteria increased after each immunization and, after the third week of treatment, were significantly higher than baseline day 0 values. This study demonstrates that oral ribosomal immunostimulation results in the production of specific salivary antibodies liable to recognize whole bacteria antigens, and therefore likely to confer protection. The kinetic analysis performed also demonstrates the rapidity of specific mucosal immune responses after oral stimulation in man, a feature still seldom explored.

Adjuvants, Immunologic↗

PubMed1998

Comparison of in vitro activity of trovafloxacin against gram-positive and gram-negative organisms with quinolones and beta-lactam antimicrobial agents.

The in vitro activity of trovafloxacin against 721 Gram-negative and 498 Gram-positive organisms was determined by the standard microdilution broth method using commercially prepared frozen microtiter plates. The activity of trovafloxacin was compared to ofloxacin, ciprofloxacin, amoxicillin/clavulanate, ampicillin/sulbactam (1:1), piperacillin/tazobactam, ceftriaxone, and imipenem. Trovafloxacin had equal or greater activity compared with the other agents tested against Citrobacter diversus, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Stenotrophomonas maltophilia, Serratia marcescens, staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, group G streptococci, Enterococcus faecalis, and E. faecium. The reliability of the commercially prepared plates for testing the in vitro activity of the quinolones was evaluated by comparing identical isolates also tested by broth microdilution using laboratory prepared plates. The commercially prepared plates generally correlated, within one- to twofold dilutions, with the laboratory prepared plates. There was, however, a large discrepancy obtained when testing Enterobacter agglomerans and E. cloacae, where the commercially prepared plates yielded a significantly higher MIC90 value.

4-Quinolones↗

PubMed2003

Comparative in vitro potency of amoxycillin-clavulanic acid and four oral agents against recent North American clinical isolates from a global surveillance study.

The in vitro activity of amoxycillin-clavulanic acid was compared with four comparator oral antimicrobial agents; ampicillin, azithromycin, cefuroxime and trimethoprim-sulphamethoxazole against 4536 recent clinical isolates covering 29 species isolated in the US and Canada between 1997 and 1999. Based upon Minimum inhibitory concentrations (MICs), amoxycillin-clavulanic acid was the most active agent against many Gram-positive species and phenotypes including methicillin susceptible Staphylococcus aureus (MSSA) Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus pneumoniae including penicillin intermediate and macrolide resistant strains and was as active as ampicillin against Streptococcus agalactiae, penicillin resistant S. pneumoniae and viridans streptococci. Against Enterobacteriaceae amoxycillin-clavulanic acid in general, displayed weak activity with only Proteus mirabilis and Proteus vulgaris displaying levels of susceptibility above the 90th percentile. Amoxycillin-clavulanic acid had significant activity against many species of Gram-negative non-Enterobacteriaceae including Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis but negligible activity against Burkholderia cepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Amoxycillin-clavulanic acid continues to retain excellent activity against the majority of targeted pathogens despite 20 years of clinical use.

Administration, Oral↗

PubMed2004

Respiratory infections and asthma: current treatment strategies.

Infections such as lower respiratory illness potentially contribute to the initiation of asthma and are major factors in recurring acute exacerbations of the condition. Although typical bacterial respiratory pathogens such as Streptococcus pyogenes, Streptococcus pneumoniae and Hemophilus influenzae do not initiate asthmatic exacerbations, data from a subgroup of adults suggest a potential role for Mycoplasma pneumoniae and Chlamydia pneumoniae in the onset of asthma. Common cold viruses, predominantly respiratory syncytial virus (RSV) in young children and rhinoviruses in older children and adults, are the major causes of acute exacerbations of asthma. These exacerbations are not prevented with maintenance therapies that are used for chronic asthma, but do respond to short courses of systemic corticosteroids. There are continued attempts to produce a successful vaccine and antiviral agents for the treatment of RSV that are more effective and more practical to use than ribavirin, which is currently the only available antiviral for RSV. The prevention and treatment of rhinovirus infections have focused on the major receptor for the virus, intercellular adhesion molecule-1 (ICAM-1), which is located on respiratory epithelial cells. A multivalent, recombinant, antibody fusion protein identified as CFY196 has high avidity for ICAM-1 and has the potential to protect against rhinovirus infection. Another approach for preventing and treating rhinovirus infection uses a recombinant, soluble, truncated form of ICAM-1 in which the transmembrane and intracellular domains of the protein have been deleted. An initial clinical study on this agent demonstrated clinical efficacy in ameliorating the symptoms of experimental rhinovirus infection in volunteers, but did not significantly prevent infection.

Acute Disease↗

PubMed1984

Synthesis and antimicrobial activity of clindamycin analogues: pirlimycin, 1,2 a potent antibacterial agent.

The preparation of a series of analogues of clindamycin is described in which the naturally occurring five-membered cyclic amino acid amide portion of the molecule is replaced by a four-, six-, or seven-membered cyclic amino acid amide. The most interesting compound is pirlimycin (7e, U-57,930E), in which the (2S-trans)-4-n-propylhygramide portion of clindamycin is replaced by (2S-cis)-4-ethylpipecolamide. This structural modification results in significantly favorable changes in toxicity, metabolism, and antibacterial potency. Although the in vitro antibacterial activity of clindamycin and pirlimycin are nearly identical, the latter compound is 2-20 times more active than clindamycin when administered to mice experimentally infected with strains of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Bacteroides fragilis, and Plasmodium berghei. Pirlimycin is absorbed in rats and mice following both subcutaneous and oral administration. It readily penetrates B. fragilis induced abscesses in mice and is sequestered within these abscesses. A drug concentration of at least 60 times the required inhibitory concentration is maintained for 6 h following a single subcutaneous dose of 200 mg/kg. Urinary excretion of total bioactivity consists only of intact pirlimycin with no other antibacterially active metabolites being detected. Pirlimycin is tolerated well in rats and mice at the administered levels.

Animals↗

PubMed1999

ClpE, a novel type of HSP100 ATPase, is part of the CtsR heat shock regulon of Bacillus subtilis.

Clp ATPases, which include the ubiquitous HSP100 family, are classified according to their structural features and sequence similarities. During the course of the Bacillus subtilis genome sequencing project, we identified a gene encoding a new member of the HSP100 family. We designated this protein ClpE, as it is the prototype of a novel subfamily among the Clp ATPases, and have identified homologues in several bacteria, including Listeria monocytogenes, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus pneumoniae, Lactobacillus sakei and Clostridium acetobutylicum. A unique feature of these Hsp100-type Clp ATPases is their amino-terminal zinc finger motif. Unlike the other class III genes of B. subtilis (clpC and clpP ), clpE does not appear to be required for stress tolerance. Transcriptional analysis revealed two sigmaA-type promoters, expression from which was shown to be inducible by heat shock and puromycin treatment. Investigation of the regulatory mechanism controlling clpE expression indicates that this gene is controlled by CtsR and is thus a member of the class III heat shock genes of B. subtilis. CtsR negatively regulates clpE expression by binding to the promoter region, in which five CtsR binding sites were identified through DNase I footprinting and sequence analysis.

Adenosine Triphosphatases↗

PubMed2001

Comparative in vitro activity of thiamphenicol-glycinate and thiamphenicol-glycinate-acetylcysteinate and other antimicrobials against respiratory pathogens.

Thiamphenicol-glycinate-acetylcysteinate (TGA; CAS 20192-91-0) is widely used for the treatment of infections of varied aetiology. The aim of this study was to compare the antibacterial activity of thiamphenicol-glycinate (TG; CAS 15318-45-3), TGA, amoxicillin (CAS 61336-70-7) plus clavulanic acid (CAS 58001-44-8), azithromycin (CAS 83905-01-5) and ceftriaxone (CAS 104376-79-6). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined against Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae according to the National Committee for Clinical Laboratory Standards (NCCLS) methods. The effects of changes in assay conditions were also examined. The activity of TG and TGA was similar to that of amoxicillin plus clavulanic acid, with the exception of methicillin resistant S. aureus. Azithromycin and ceftriaxone were characterised by a limited activity against gram-positive cocci and methicillin resistant and cefinase-positive S. aureus, respectively. TG and TGA are characterized by a wide spectrum of activity, comparable to that of recent commercialized antibiotics for treatment of respiratory tract infections.

Acetylcysteine↗

PubMed2004

Comparative analysis of gene expression among low G+C gram-positive genomes.

We present a comparative analysis of predicted highly expressed (PHX) genes in the low G+C Gram-positive genomes of Bacillus subtilis, Bacillus halodurans, Listeria monocytogenes, Listeria innocua, Lactococcus lactis, Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Clostridium acetobutylicum, and Clostridium perfringens. Most enzymes acting in glycolysis and fermentation pathways are PHX in these genomes, but not those involved in the TCA cycle and respiration, suggesting that these organisms have predominantly adapted to grow rapidly in an anaerobic environment. Only B. subtilis and B. halodurans have several TCA cycle PHX genes, whereas the TCA pathway is entirely missing from the metabolic repertoire of the two Streptococcus species and is incomplete in Listeria, Lactococcus, and Clostridium. Pyruvate-formate lyase, an enzyme critical in mixed acid fermentation, is among the highest PHX genes in all these genomes except for C. acetobutylicum (not PHX), and B. subtilis, and B. halodurans (missing). Pyruvate-formate lyase is also prominently PHX in enteric gamma-proteobacteria, but not in other prokaryotes. Phosphotransferase system genes are generally PHX with selection of different substrates in different genomes. The various substrate specificities among phosphotransferase systems in different genomes apparently reflect on differences in habitat, lifestyle, and nutrient sources.

Energy Metabolism↗

PubMed1994

The type I macrophage scavenger receptor binds to gram-positive bacteria and recognizes lipoteichoic acid.

Macrophage scavenger receptors exhibit unusually broad binding specificity for polyanionic ligands and have been implicated in atherosclerosis and various host defense functions. Using a radiolabeled, secreted form of the type I bovine macrophage scavenger receptor in an in vitro binding assay, we have found that this receptor binds to intact Gram-positive bacteria, including Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus, Enterococcus hirae, and Listeria monocytogenes. Competition binding studies using purified lipoteichoic acid, an anionic polymer expressed on the surface of most Gram-positive bacteria, show that lipoteichoic acids are scavenger receptor ligands and probably mediate binding of the receptor to Gram-positive bacteria. Lipoteichoic acids, for which no host cell receptors have previously been identified, are implicated in the pathogenesis of septic shock due to Gram-positive bacteria. Scavenger receptors may participate in host defense by clearing lipoteichoic acid and/or intact bacteria from tissues and the circulation during Gram-positive sepsis. Since scavenger receptors have been previously shown to bind to and facilitate bloodstream clearance of Gram-negative bacterial endotoxin (lipopolysaccharide), these receptors may provide a general mechanism for macrophage recognition and internalization of pathogens and their cell surface components.

Animals↗

PubMed1978

Clinical and laboratory evaluation of cefamandole in infants and children.

Fifty-three infants and children, aged three months to 15 years, were treated with an average daily dose of 100 mg of cefamandole/kg intravenously. Of these patients, 47 had soft tissue cellulitis and six had pneumonia. Primary pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, were isolated from 43 of the 53 patients. Bacteremia was documented in six of the 53 patients. A satisfactory clinical and bacteriologic response to cefamandole was achieved in all cases except on (98%). The only treatment failure occurred in an infant with both periorbital cellulitis and bacteremia due to H. influenzae who developed meningitis while receiving cefamandole; no extravasation of the drug across the blood-brain barrier could be detected in spite of inflamed meninges. In general, the only aberrant effects of cefamandole were the appearance of eosinophilia in 28% of patients and a positive indirect Cooms' test without hemolysis in one patient. Cefamandole showed excellent in vitro activity against 87 ampicillin-resistant strains of H. influenzae. Because it has greater activity than any of the other cephalosporins against this important pediatric pathogen, cefamandole may have particular pertinence in the treatment of infections in infants and young children.

Adolescent↗

PubMed1998

Serum bactericidal activity of newer oral cephalosporins in healthy volunteers.

The serum bactericidal activity of three oral cephalosporins was studied in 12 volunteers, after administration of single doses of cefuroxime axetil 250 mg, cefixime 200 mg, cefixime 400 mg and cefetamet pivoxil 500 mg. Serum bactericidal activity against clinical isolates of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae was measured by a standardized microdilution method. Cefuroxime axetil demonstrated the best bactericidal activity against Gram-positive organisms and cefixime was the most bactericidal against Gram-negative bacteria.

Administration, Oral↗

PubMed2001

In vitro activity of linezolid and 11 other antimicrobials against 566 clinical isolates and comparison between NCCLS microdilution and Etest methods.

The in vitro activity of linezolid and 11 other antimicrobials was determined for 566 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, some of them resistant to several antibiotics, using a broth microdilution method and the Etest method. All Gram-positive organisms tested were inhibited by a concentration of <or=4 mg/L of linezolid, including methicillin-resistant staphylococci, vancomycin- and ampicillin-resistant enterococci, and penicillin-intermediate and -resistant pneumococci. MICs of linezolid by the Etest method were usually one to two dilution values lower than those obtained by microdilution.

Acetamides↗

PubMed2001

Susceptibility of a variety of clinical isolates to linezolid: a European inter-country comparison.

Using standardized in vitro susceptibility tests, 3382 bacteria recently isolated from skin, blood or respiratory tract infections were analysed for their susceptibility to linezolid, a new oxazolidinone, and a number of comparator antibacterial agents. Isolates originated in France, Italy, Germany, Spain, Sweden, The Netherlands and the UK. Laboratories in each country independently conducted broth microdilution susceptibility tests using NCCLS methods and epsilonometry (Etest). Isolates of Gram-positive cocci tested in each laboratory included methicillin-susceptible and -resistant Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae and Enterococcus spp. Isolates of Moraxella catarrhalis and Haemophilus influenzae were also included. Where appropriate, comparator drugs (oxacillin, vancomycin, gentamicin, co-amoxiclav, ciprofloxacin, erythromycin, penicillin G, clindamycin and ampicillin) were also tested. Linezolid demonstrated excellent activity against all of the Gram-positive cocci with MIC50s ranging from 0.5 to 4 mg/L. The drug demonstrated only modest activity against M. catarrhalis and H. influenzae with MIC50s ranging from 4 to 16 mg/L.

Acetamides↗

PubMed2000

The gene encoding IIAB(Man)L in Streptococcus salivarius is part of a tetracistronic operon encoding a phosphoenolpyruvate: mannose/glucose phosphotransferase system.

Glucose and mannose are transported in streptococci by the mannose-PTS (phosphoenolpyruvate:mannose phosphotransferase system), which consists of a cytoplasmic IIAB protein, called IIAB(Man), and an uncharacterized membrane permease. This paper reports the characterization of the man operon encoding the specific components of the mannose-PTS of Streptococcus salivarius. The man operon was composed of four genes, manL, manM, manN and manO. These genes were transcribed from a canonical promoter (Pman) into a 3.6 kb polycistronic mRNA that contained a 5'-UTR (untranslated region). The predicted manL gene product encoded a 35.5 kDa protein and contained the amino acid sequences of the IIA and IIB phosphorylation sites already determined from purified S. salivarius IIAB(Man)L. Expression of manL in Escherichia coli generated a 35 kDa protein that reacted with anti-IIAB(Man)L antibodies. The predicted ManM protein had an estimated size of 27.2 kDa. ManM had similarity with IIC domains of the mannose-EII family, but did not possess the signature proposed for mannose-IIC proteins from Gram-negative bacteria. From multiple alignment analyses of sequences available in current databases, the following modified IIC(Man) signature is proposed: GX3G[DNH]X3G[LIVM]2XG2[STL][LT][EQ]. The deduced product of manN was a hydrophobic protein with a predicted molecular mass of 33.4 kDa. The ManN protein contained an amino acid sequence similar to the signature sequence of the IID domains of the mannose-EII family. manO encoded a 13.7 kDa protein. This gene was also transcribed as a monocistronic mRNA from a promoter located in the manN-manO intergenic region. A search of current databases revealed the presence of IIAB(Man)L, ManM, ManN and ManO orthologues in Streptococcus mutans, Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis. This work has elucidated the molecular structure of the mannose PTS in streptococci and enterococci, and demonstrated the presence of a putative regulatory protein (ManO) within the man operon.

Amino Acid Sequence↗