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[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1989). II. Background of patients].

Clinical background was investigated on 1,197 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period from June, 1989 to May, 1990. 1. Distribution of sex and age A majority of female patients with UTIs accounted for a twenties and thirties. The proportion of male patients with UTI has increased with age, accounting for majority in patients 70 years or older. 2. Distribution of infection types and age Most cases among twenties or thirties were uncomplicated UTIs. Fifties and older cases were most frequent in complicated UTIs. 3. Distribution of isolated bacteria and age Escherichia coli was most frequent on the whole, followed by Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus spp. and Klebsiella spp.. E. coli had declined with age, and on the other hand, E. faecalis and P. aeruginosa had increased with age. 4. Administration of antibiotics and pathogens isolated from UTIs. In uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from patients have obviously decreased from 439 to 4. Before an administration of antibiotics, E. coli was mainly detected, but after an administration of antibiotics, E. coli has decreased into two strains. After administration of antibiotics, pathogens of complicated UTIs, without indwelling catheter, have decreased from 324 to 19: E. coli has decreased from 86 to 2, but E. faecalis, Staphylococcus spp., Enterobacter spp. and P. aeruginosa have increased. Pathogens of complicated UTIs with indwelling catheter, have decreased from 156 to 14 after administration of antibiotics, and mainly isolated pathogens were E. faecalis and P. aeruginosa.

Adolescent↗

Antimicrobial activity and biocompatibility of polyurethane and silicone catheters containing low concentrations of silver: a new perspective in prevention of polymer-associated foreign-body-infections.

In modern medicine, infection is one of the most serious complications of implanted plastic devices. The host is not able to overcome this special type of opportunistic infection despite having a normal immune response and a low virulence of most of the bacteria involved. Antimicrobial therapy alone generally cannot cure the infection and the removal of catheters often remains the only choice of therapy. Bacterial adhesion to the polymer surface of the catheter, be it luminal or external, is an important step in the pathogenesis of catheter-associated infections. In this report, we describe new approaches to the prevention of infections by impregnation of polyurethane and silicone with silver by two different methods. The antimicrobial activity of these silver-impregnated catheters is more than 10 fold higher for coagulase-negative staphylococci (CNS) compared to catheters without silver. Similar results are obtained with other microbial organisms like Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The new polymers show no cytotoxic or thrombogenic side effects in vitro.

Anti-Bacterial Agents↗

An in-vitro investigation of the antibacterial effect of nisin in root canals and canal wall radicular dentine.

AIM: To determine whether nisin, a bacteriocin, would be effective at killing Enterococcus faecalis and Streptococcus gordonii cells in solution and within the root canal system. METHODOLOGY: Bacterial isolates of E. faecalis and S. gordonii were grown from glycerol stocks in closed tubes containing BHY broth at 37 degrees C. The minimum bactericidal concentration (MBC) of nisin for both bacterial species was determined by a microdilution method. Extracted human teeth were decoronated to produce roots of equal length with a single canal and divided into six groups of 10 roots. The canals were prepared to a master apical size 30 file using 0.04 taper Ni-Ti rotary instruments. Bacterial samples of each species were inoculated into three groups of prepared roots and incubated in closed tubes at 37 degrees C for 21 days. The root canals in each group were then medicated with water (control), calcium hydroxide powder mixed with sterile water [Ca(OH)2], or nisin and incubated for a further 7 days. Rotary Ni-Ti files were used to take radicular dentine samples from the walls of each canal which were then incubated in BHY broth for 24 h. Optical density (OD600) readings were taken as a measure of bacterial growth. RESULTS: The MBC of nisin for E. faecalis and S. gordonii was 70 and 20 mg mL(-1) respectively. Calcium hydroxide and nisin medication eradicated infection within the root canal while cells remained viable in the control group. Mean optical density (OD600) readings from canal wall dentine shavings infected with E. faecalis were 1.32 +/- 0.98, 0.73 +/- 0.27 and 0.69 +/- 0.38 for the control, Ca(OH)2 and nisin samples respectively. Corresponding mean readings for S. gordonii were 1.19 +/- 0.18, 0.73 +/- 0.15 and 0.60 +/- 0.29. The Ca(OH)2 and nisin group readings were significantly (P < 0.01) lower than the control for each species as tested by Student's t-test and Mann-Whitney U statistical analysis. Values for Ca(OH)2 and nisin were not significantly (P > 0.01) different. CONCLUSION: Nisin was effective at eradicating E. faecalis and S. gordonii cells in pure culture and was comparable with Ca(OH)2 in the elimination of these species from within the root canal system.

Anti-Bacterial Agents↗

Detection of bacteria in endodontic samples by polymerase chain reaction assays and association with defined clinical signs in Italian patients.

BACKGROUND/AIMS: The presence of selected bacteria (Enterococcus faecalis, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis, Treponema denticola) in infected root canals was studied using polymerase chain reaction (PCR) assays, and the association of bacteria with clinical signs of endodontic disease was assessed. The null hypothesis, that no difference could be observed between clinical signs of apical periodontitis and a specific bacterial strain, was tested. METHODS: Microbial samples were obtained from 62 teeth in 54 patients with endodontic disease. For each tooth, clinical data including patient symptoms were collected. Teeth were categorized by diagnosis as having acute apical periodontitis (AAP, teeth with clinical symptoms but no periapical radiolucency, n=22), chronic apical periodontitis (CAP, teeth with radiolucency but no clinical symptoms, n=15) or exacerbated apical periodontitis (EAP, teeth with symptoms and radiolucency, n=25). Seventy-one percent of cases were primary endodontic infections, and 29% were recurrent ('secondary') endodontic infections (failing cases). PCR assays were used to detect the presence of the selected bacteria. RESULTS: T. denticola and E. faecalis were each detected in 15 of 62 samples (24%), P. gingivalis in 8 samples (13%), P. intermedia in 5 samples (8%), and T. forsythensis in 4 samples (7%). T. denticola was detected in 56% of teeth with EAP. E. faecalis was found in 60% of teeth with CAP and in 72% of teeth with secondary infection. Statistical analysis demonstrated an association of CAP and secondary endodontic infection with the presence of E. faecalis. (P<0.01). EAP was associated with the presence of T. denticola (P<0.01). CONCLUSION: T. denticola was associated with symptomatic endodontic disease in the presence of apical bone resorption. E. faecalis was associated with treatment failures. We suggest that these species may play critical roles in endodontic pathology.

Adult↗

Inability of cephalothin testing to predict cefprozil susceptibility.

The 30-micrograms cefprozil disk and the cephalosporin class (30-micrograms cephalothin) disk were compared for their abilities to predict cefprozil susceptibility by agar disk diffusion testing. High error (5.02% major and 14.11% minor) rates were encountered with the cephalothin disk and were most frequently observed for Escherichia coli and Enterococcus faecalis. The cefprozil disks resulted in rates of 0.05% very major, 0% major, and 3.72% minor errors. Thus, the 30-micrograms cefprozil disk is more desirable for predicting cefprozil susceptibility.

Cephalosporins↗

Effect of nutrient composition on the in vitro growth of urogenital lactobacilli and uropathogens.

Previous clinical studies have shown that nutrients and probiotic agents can alter the composition of the vaginal flora. The present in vitro study has shown that uropathogens have a growth advantage over lactobacilli, but potentially there are natural substances that could be applied vaginally to stimulate lactobacilli growth to the detriment of the pathogens. When chemically defined medium representative of vaginal fluid at pH 5.5 was supplemented with skim milk, it acted as a better substrate for Lactobacillus rhamnosus GR-1 than for uropathogenic bacteria and Candida albicans. Lactobacillus MRS medium, even at pH 4.5, supports the growth of pathogens, but when supplemented with ascorbic acid or EDTA, Lactobacillus growth was significantly higher. When L. rhamnosus GR-1 was coincubated in a combined nutrient composition of vitamins and lactose, it survived better than Escherichia coli and Enterococcus faecalis. These in vitro results provide a basis for testing nutritional supplements to alter the urogenital flora in an attempt to enhance restoration and maintenance of a normal disease-free state.

Animals↗

Identification and characterization of a mobilization gene in the streptococcal plasmid, pVA380-1.

The 4.2-kb cryptic streptococcal plasmid, pVA380-1, has a broad host range and replicates via a rolling circle mode. The nucleotide base sequence of the 2.5-kb basic replicon of this plasmid, containing a plus origin, a minus origin, and a rep gene, was reported previously. The completed nucleotide base sequence of pVA380-1 revealed the presence of two additional open reading frames, ORF2 and ORF3. The protein predicted by ORF2 shared 74% amino acid identity with the Mob protein of the Group B streptococcal plasmid, pMV158. The 170 bases immediately 5' to ORF2 and to mob of pMV158 shared 87% homology and included a putative -10 region and a RSa site. A derivative of pVA380-1 into which a kanamycin resistance gene was inserted outside of the above 170 base region and ORF2 was mobilized by the conjugative streptococcal plasmid, pAM beta 1, into Enterococcus faecalis and Streptococcus sobrinus. Interruption of ORF2 by the same kanamycin resistance gene abolished the mobilizability of pVA380-1.

Amino Acid Sequence↗

Combination effect of meropenem with aminoglycosides and teicoplanin on Pseudomonas and enterococci.

The in vitro activity of meropenem, a new carbapenem, and the combination effect with netilmicin, tobramycin, gentamicin, and teicoplanin against Pseudomonas spp. and enterococci was studied. Meropenem showed very good in vitro activity against Pseudomonas aeruginosa (MIC90 2 mg/l) and good to moderate activity against Pseudomonas putida (MIC90 4 mg/l) and Enterococcus faecalis (MIC90 8 mg/l). Aminoglycosides were highly active against P. putida (MIC90 0.5 mg/l), but showed only moderate activity against P. aeruginosa. The synergistic effect of meropenem was shown in combination with teicoplanin against E. faecalis (40%). No Pseudomonas strains were inhibited by the synergistic effect of meropenem with aminoglycosides. No antagonism occurred with any of the combinations.

Aminoglycosides↗

Synthesis and antibacterial activities of chiral 1,3-oxazinan-2-one derivatives.

We report here the design, synthesis, and antibacterial activities of novel classes of compounds containing chiral 1,3-oxazinan-2-ones and oxazolidinones as the basic core structures. These compounds are tertiary amines containing the core structures and two aryl substituents. Several of these molecules exhibit potent antibacterial activities against the tested Gram-positive bacteria, including Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis. These compounds represent new structure scaffolds and can be further optimized to give new antibacterial agents with structures significantly different from those of existing classes of antibiotics.

Anti-Bacterial Agents↗

Activity of gatifloxacin and ciprofloxacin in combination with other antimicrobial agents.

The influence of non-quinolone antimicrobial agents on the antibacterial activities of gatifloxacin and ciprofloxacin was determined using chequerboard, fractional inhibitory concentration, (FIC) and time-kill analysis methods. In the chequerboard method, the quinolones were tested in combination with ten antimicrobial agents (macrolides, aminoglycosides, beta-lactams, vancomycin, rifampicin and chloramphenicol) against five bacterial strains (one strain each of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus pneumoniae). In no incidence was antagonism (FIC > or = 4) or synergy (FIC < or = 0.5) observed; all dual drug combinations involving gatifloxacin or ciprofloxacin showed additivity/indifference (FIC > 0.5, < 4). By time-kill analysis, the strains were tested at a quinolone concentration equal to 8 x MIC in combination with a second antibiotic at 0.5xits MIC. These combinations killed non-enterococcal strains at rates similar to those with quinolones alone. However, rifampicin and chloramphenicol were often antagonistic (100-fold lesser killing) to the lethal action of gatifloxacin and ciprofloxacin against E. faecalis. These findings indicate that, with the exception of E. faecalis, the antibacterial activities of quinolones are generally additive/indifferent to those of other antimicrobial agents.

Anti-Bacterial Agents↗

Separation and isolation of viable bacteria by capillary zone electrophoresis.

Mixtures of bacteria, Enterococcus faecalis (ATCC 29212), Streptococcus pyogenes (ATCC 19615), Streptococcus agalactiae (ATCC 13813), Streptococcus pneumoniae (ATCC 6303), and Staphylococcus aureus (ATCC 29213), were resolved into discrete electrophoretic bands using capillary zone electrophoresis (CZE). Bacteria remained viable (> 90%) during the electrophoretic process. Analysis of peak separation indicates organisms were quantitatively resolved and recovered at greater than 98% purity. E. faecalis was resolved into two discrete fractions with different chain assemblages that may reflect different developmental stages. These findings suggest that CZE can afford the microbiologist a new tool for studying the composition and distribution of microorganisms in mixed populations.

Electrophoresis↗

Inactivation of local root canal medicaments by dentine: an in vitro study.

AIMS: The aim of the study was to investigate the inactivation by dentine of the antibacterial activity of various commonly used local root canal medicaments. METHODOLOGY: The medicaments tested were saturated calcium hydroxide solution, 1% sodium hypochlorite, 0.5% and 0.05% chlorhexidine acetate, and 2/4% and 0.2/0.4% iodine potassium iodide. Dentine was sterilized by autoclaving and crushed into powder with a particle size of 0.2-20 microns. Aliquots of dentine suspension were incubated with the medicaments in sealed test tubes at 37 degrees C for 24 h or 1 h before adding the bacteria. In some experiments bacteria were added simultaneously with dentine powder and the medicament. Enterococcus faecalis A197A was used as a test organism. Samples for bacterial culturing were taken from the suspensions at 5 min, 1 h and 24 h after adding the bacteria. RESULTS: Dentine powder had an inhibitory effect on all medicaments tested. The effect was dependent on the concentration of the medicament as well as on the length of the time the medicament was preincubated with dentine powder before adding the bacteria. The effect of calcium hydroxide on E. faecalis was totally abolished by the presence of dentine powder. Similarly, 0.2/0.4% iodine potassium iodide lost its effect after preincubation for 1 h with dentine before adding the bacteria. The effect of 0.05% chlorhexidine and 1% sodium hypochlorite on E. faecalis was reduced but not totally eliminated by the presence of dentine. No inhibition could be measured when full strength solutions of chlorhexidine and iodine potassium iodide were used in killing E. faecalis. CONCLUSIONS: The dentine powder model appears to be an efficient tool for the study of interactions between local endodontic medicaments, dentine, and microbes.

Anti-Infective Agents, Local↗

2'-Chloropentostatin: discovery, fermentation and biological activity.

2'-Chloropentostatin (2-CP) is a new nucleoside antibiotic produced by Actinomadura sp. ATCC 39365. A selectively sensitive assay organism, Enterococcus faecalis PD 05045 (MIC 0.005 micrograms/ml) was instrumental in the discovery of this compound. 2-CP is a tight-binding inhibitor of adenosine deaminase (Ki = 1.1 X 10(-10) M).

Actinomycetales↗

The origin of transfer (oriT) of the enterococcal, pheromone-responding, cytolysin plasmid pAD1 is located within the repA determinant.

The highly conjugative pAD1 plasmid encodes a mating response to the peptide sex pheromone cAD1 secreted by recipient strains of Enterococcus faecalis. The location of the origin of transfer (oriT) was determined through the ability to mobilize the Escherichia coli-E. faecalis shuttle plasmid pAM401 carrying specific segments of pAD1. The oriT sequence was found to be completely within the repA determinant known to be required for plasmid maintenance.

Bacterial Proteins↗

Esophageal erosion as a possible bacterial entry site in an acute lymphoblastic leukemia patient with sepsis.

A 69-year-old man with relapsed acute lymphoid leukemia was treated with adriamycin, vincristine, and prednisolone. During this chemotherapy, the patient developed sepsis and meningitis. Although many kinds of antimicrobial drugs, including imipenem, meropenem, amphotericin-B, and gamma-globulin were administered, the patient died of respiratory failure. A positive result for Enterococcus faecalis was obtained in both blood and cerebrospinal fluid culture. Autopsy revealed multiple small erosions in the lower esophagus. Histopathological examination showed multiple nuclear inclusion bodies of herpes simplex virus in the squamous epithelial cells at the edge of the erosions. Moreover, proliferation of micrococci was observed at the base of the erosions and in the lumina of the submucosal small vessels. These findings suggested that E faecalis entered the blood circulation from this lesion. In many patients with febrile neutropenia, the pathogenesis of infection remains unclear. Our case seems significant for clarifying the focus and pathogenesis of febrile neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗

Pulvinones as bacterial cell wall biosynthesis inhibitors.

Pulvinones were synthesized (>180) in arrays and evaluated as inhibitors of early stage cell wall biosynthesis enzymes MurA-MurD. Several pulvinones inhibited Mur enzymes with IC(50)'s in the 1-10 microg/mL range and demonstrated antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphyloccus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae.

Anti-Bacterial Agents↗

Serum inhibitory titers and serum bactericidal titers for human subjects receiving multiple doses of the antibacterial oxazolidinones eperezolid and linezolid.

In Phase I trials subjects received multiple doses of eperezolid (PNU-100592; formerly U-100592) and linezolid (PNU-100766; formerly U-100766), and steady-state samples were drawn at the projected peak and trough timepoints. Serum inhibitory titer and serum bactericidal titer values were determined using single strains of Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. Serum inhibitory titer values generally correlated with drug concentration in serum and inherent organism susceptibility. Against S. aureus and E. faecalis sera from patients dosed with either drug were generally inhibitory at the peak timepoint, but at trough only linezolid exhibited a persistent effect. No bactericidal activity was seen for either drug against S. aureus or E. faecalis. The sera from patients dosed with either drug exhibited inhibition of S. pneumoniae at peak and trough. Bactericidal activity was seen against S. pneumoniae for both drugs at peak time and at trough for many of the sera for patients on the higher dose regimens. The results demonstrated that the sera from most human subjects dosed with eperezolid or linezolid were inhibitory to S. aureus and E. faecalis and S. pneumoniae and that many of the samples exhibited bactericidal activity for S. pneumoniae.

Acetamides↗

In vitro resistance to platelet microbicidal protein correlates with endocarditis source among bacteremic staphylococcal and streptococcal isolates.

Traditionally, platelets have been thought to contribute to the induction and propagation of infective endocarditis (IE). However, recent studies suggest that platelets may potentially mitigate IE via secretion of alpha-granule-derived platelet microbicidal protein (PMP). In this study, we compared the PMP susceptibility of bacteremic isolates from patients with and without IE. Isolates of Staphylococcus aureus (n = 17), coagulase-negative staphylococci (CNS; n = 28), viridans streptococci (VS; n = 54), and Enterococcus faecalis (n = 20), each at a final inoculum of 2 x 10(3) CFU/ml, were exposed to PMP [100 U/ml, (5 micrograms/ml)] for 2 h, and the percent survival was determined. For S. aureus, CNS, and VS isolates, there was a significant correlation between an IE source and increased percent survival post-PMP exposure; the mean percent survivals of S. aureus, CNS, and VS were significantly greater for IE versus non-IE isolates (P < 0.005 for each organism). No significant correlation was observed between the source of bacteremic E. faecalis isolates and PMP susceptibility. These data suggest that staphylococcal and VS (but not enterococcal) resistance to PMP may facilitate either the induction or progression of IE.

Animals↗