Prophylactic vancomycin in very-low-birthweight infants.
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Humans↗
Biomedical subjects
D Greenwood
Publications and source records attributed to D Greenwood.
Localization of cholinergic and purinergic receptors on outer hair cells isolated from the guinea-pig cochlea.
Acetylcholine (ACh) and adenosine 5'-triphosphate (ATP) are shown to act in opposing fashion on guinea-pig cochlear outer hair cells (OHCS) via receptors localized within different fluid compartments of the organ of Corti. The cholinergic (efferent) receptors localized at the basal (perilymphatic) region of these cells activated a rapidly desensitizing hyperpolarizing K+ current. In contrast, purinergic (ATP) receptors were localized at the apical (endolymphatic) surface of OHCS and activated a depolarizing nonselective cation current which exhibited inward rectification and lacked desensitization. Localization of the receptors was determined by using whole-cell patch-clamp, by recording onset latencies and response amplitudes to pulses of either ACh or ATP pressure-applied at selected sites along the length of isolated OHCS. Under voltage-clamp at -60 mV, the largest ACh-induced (outward) currents were recorded when ACh was directed at the basal region of the cells. Conversely, the maximum (inward) ATP currents were obtained when ATP was directed toward the apical surface of these cells. Onset latencies increased rapidly from a minimum of approximately 10 ms for either ACh or ATP as the drug pipette was moved away from these optimal sites. The ATP response was antagonized by amiloride in a dose-dependent manner with a KD of approximately 400 microM. The localization of P2-type purinoceptors to the endolymphatic surface of OHCS suggests that ATP mediates a humoral modulation of the mechano-electrical transduction process.
Acetylcholine↗
The comparative activity of fosfomycin trometamol against organisms isolated from infected urines.
Five hundred urinary pathogens, collected from patients of general practitioners and hospital in-patients, were identified and tested for susceptibility to fosfomycin, ampicillin, cephalexin, nalidixic acid, nitrofurantoin, trimethoprim and sulfamethoxazole. Overall, 83% of the isolates were sensitive to fosfomycin, comprising 89% of the out-patient strains and 77% of the in-patient isolates. This degree of sensitivity was similar to that of cephalexin, nalidixic acid and trimethoprim, but higher than that observed with ampicillin, nitrofurantoin and sulfamethoxazole. Fosfomycin generally showed a broad spectrum of activity, but was less active than some other compounds against Klebsiella spp. and streptococci. More than 70% of strains resistant to ampicillin, sulfamethoxazole or trimethoprim were sensitive to fosfomycin indicating that cross resistance is not presently a problem.
Anti-Bacterial Agents↗
The influence of anaerobiosis on the activity of fosfomycin trometamol.
MICs of fosfomycin trometamol were estimated for 40 strains of bacteria (20 gram-positive cocci, 20 gram-negative bacilli) by the agar incorporation method (Iso-Sensitest agar) in the presence of the potentiating agent, glucose-6-phosphate (25 mg/l). Titrations were carried out in duplicate under aerobic and anaerobic conditions. For 22 strains (12 gram-negative bacilli), a fourfold or greater reduction in MIC was observed in tests conducted under anaerobic conditions. The effect was particularly marked with Klebsiella spp., four of five strains of which showed a 16- to 32-fold reduction in MIC in anaerobic conditions. To investigate the reasons for the effect of anaerobiosis, selected strains were examined in an opacity monitoring device in which cultures can be grown in aerobic or anaerobic atmosphere. Surprisingly, the effect of anaerobiosis observed by continuous turbidimetric monitoring was much less than that seen in agar incorporation MIC titrations: under anaerobic conditions, there was little or no reduction in the concentration of fosfomycin trometamol required to cause a lytic effect on dense bacterial cultures, and a small, but variable effect on the emergence of resistant variants.
Anaerobiosis↗
The quinine connection.
Quinine, an alkaloid derived from the bark of the cinchona tree was brought to Europe from Peru in the 17th century. Isolation of quinine and other cinchona alkaloids was achieved in France in the early part of the 19th century and uncertainties of supply of the bark stimulated efforts to synthesize quinine. While attempting synthesis, the young chemist, William H. Perkin, stumbled on mauve purple, the first aniline dye. Use of dyes in histopathology and the infant specialty of medical microbiology established the reputation of Paul Ehrlich, and partial success with the use of dyes in trypanosomiasis and malaria encouraged the German dye industry to pursue these substances as antimicrobial agents. By good fortune, this led to the discovery of the sulphonamides by Gerhard Domagk in the mid-1930s, an event that stimulated much other work and may have influenced the development of antibiotics.
Europe↗
An investigation of beta-lactamases from clinical isolates of Bacteroides species.
Among a group of 116 clinically significant isolates of Bacteroides spp., 24 exhibited beta-lactamase activity greater than the basal level characteristic of most Bacteroides strains. Investigation of specific enzyme activity, iso-electric point and enzyme inhibition profiles revealed that the beta-lactamases involved could be divided into four groups, some showing similarity to those described in previous studies. Seven of the enzymes were able to hydrolyse cefoxitin, latamoxef or imipenem, and eight enzymes degraded penicillin in the presence of clavulanic acid. Five strains showed reduced susceptibility to cefoxitin, latamoxef or imipenem which was not associated with beta-lactamase activity.
Anti-Bacterial Agents↗
Effect of inoculum size on bacteriolytic activity of cefminox and four other beta-lactam antibiotics against Escherichia coli.
MICs and turbidimetric experiments revealed a negligible inoculum effect with two Escherichia coli strains exposed to cefminox and cefoxitin, whereas a marked inoculum effect was revealed after exposure to cefotaxime, ceftizoxime, and imipenem. The activities of the cephamycins were associated with spheroplast formation and bacteriolysis at concentrations close to the MIC, whereas the other agents induced the formation of filaments or, in the case of imipenem, rounded cells.
Anti-Bacterial Agents↗
An overview of neural networks.
Some of the world's leading researchers in neural networks submitted their most recent results concerning their research in neural networks to the author for inclusion in this survey. Descriptive accounts of their collective papers are presented as well as a list of sources of information concerning neural networks, such as journals, books, and technical reports. The material is broken into categories related to established areas in computer science, robotics, neural modeling, and engineering.
Algorithms↗
Phenotypic variability and sensitivity tests: carry on regardless.
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Bacteria↗
Comparative susceptibility of cefminox and cefoxitin to beta-lactamases of Bacteroides spp.
The susceptibility of the new cephamycin antibiotic, cefminox, to hydrolysis by various types of beta-lactamase produced by organisms of the Bacteroides fragilis group was compared with that of cefoxitin. Several enzymes were able to achieve complete hydrolysis of both drugs during overnight incubation, but no marked difference between the rates of inactivation of cefminox and cefoxitin was observed. Susceptibility of the cephamycins to crude extracts of beta-lactamases from the test strains of Bacteroides spp. did not correlate with the results of conventional minimum inhibitory concentration titrations. Possible reasons for these discrepancies are discussed.
Bacteroides fragilis↗
Turbidimetric study of the effect of inoculum density on the response of Escherichia coli to gentamicin under aerobic and anaerobic conditions.
The turbidimetric response to gentamicin of two strains of Escherichia coli was examined under aerobic and anaerobic conditions with 3 inocula. Turbidimetry showed that the minimum inhibitory concentration (MIC) was influenced by growth of partially inhibited cultures during the overnight incubation period. Continuous turbidimetric monitoring also allowed the minimum antibacterial concentration (MAC: the lowest concentration to cause an effect on normal growth) to be measured. As judged by the MAC, the effect of inoculum was small over the range 5 x 10(5) to 9 x 10(7) colony-forming units (CFU), but increased substantially as the inoculum was raised further. Exposure to gentamicin under anaerobic conditions caused an average 4-fold rise in the MAC with different inocula.
Aerobiosis↗
Fosfomycin trometamol: activity in vitro against urinary tract pathogens.
The spectrum of activity of fosfomycin embraces all the common causes of uncomplicated urinary tract infection. The activity is greatly affected by the conditions of the test. Glucose, phosphates and NaCl all interfere with the activity of the drug, whereas glucose-6-phosphate has a marked potentiating effect against many strains. The activity of fosfomycin is greater at acid than at alkaline pH; inoculum density also has an effect, but this is less marked at acid pH values. Fosfomycin is rapidly bactericidal to susceptible bacteria, causing lysis within 30 min. In contrast, fosmidomycin, which also has a narrower spectrum of activity than fosfomycin, is much more slowly bactericidal. In the form of its trometamol salt, fosfomycin is well absorbed after oral administration, and is excreted in high concentration in the urine. Experiments in an in-vitro model of the treatment of bacterial cystitis suggest that concentrations of fosfomycin achievable in urine after oral administration of high doses of the trometamol salt have a marked suppressive effect on bacterial growth without favouring the emergence of resistant mutants.
Biological Availability↗
Differential response to benzylpenicillin in vivo of tolerant and non-tolerant variants of Streptococcus sanguis II.
A variant that was highly tolerant to benzylpenicillin was obtained from a non-tolerant clinical isolate of Streptococcus sanguis II by repeated exposure to penicillin. The rabbit model of endocarditis was used to investigate the efficacy of a high dose regimen of benzylpenicillin (250 mg/kg; peak serum concentration c. 25 mg/l) in the prophylaxis and treatment of endocarditis during challenge or infection with the non-tolerant parent strain or its tolerant variant. The two strains exhibited a similar capacity to initiate infection. A single dose of penicillin administered 0.5 h before bacterial challenge protected six of nine rabbits infected with the non-tolerant parent strain, but none of nine infected with the tolerant variant. Treatment of established infection with penicillin administered twice daily for four days cured eight of 13 (61%) rabbits infected with the non-tolerant parent strain, but only one of 14 (7%) rabbits infected with the tolerant variant. These results support the view that tolerance to penicillin has therapeutic implications.
Drug Tolerance↗
Antibiotic resistance in enterococci in Nottingham.
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Anti-Bacterial Agents↗
Effect of growth conditions and storage on the specific activity of beta-lactamases of Bacteroides spp.
The influences of growth conditions and cold storage on the specific activity of beta-lactamases of four strains of Bacteroides spp. was studied. Interbatch variation was observed in extracts prepared in an identical way on separate occasions but less variation was observed in extracts prepared from bacteria grown on Brain Heart Infusion agar supplemented with yeast extract, haemin and menadione, than in similar extracts of bacteria grown in broth or on other solid media. The loss of enzyme activity seen during the stationary phase of growth of some strains in broth was minimal during incubation for 48 h on agar. Storage of enzyme extracts at 4 degrees C was associated with loss of enzyme activity, but activity was retained during storage at -70 degrees C for up to 32 days. Freezing and thawing had little effect on enzyme activity.
Bacteroides↗
Studies on the emergence of resistance to lomefloxacin in vitro.
The emergence of resistance to lomefloxacin, norfloxacin and ciprofloxacin was investigated in nalidixic acid sensitive and resistant urinary isolates by continuous turbidimetry. A decline in susceptibility was observed after a single exposure to each of the drugs, and further increments of resistance occurred during three sequential passages. Variants resistant to one quinolone were cross-resistant to the others. The level of resistance selected by norfloxacin in three of the five test strains was greater than that observed with lomefloxacin or ciprofloxacin. In experiments in a model of the treatment of bacterial cystitis, concentrations of lomefloxacin well within those readily achievable in urine suppressed growth of nalidixic acid sensitive and resistant strains for more than 20 h without causing any decline in susceptibility of surviving bacteria.
Anti-Infective Agents↗
Scanning electronmicroscopy of Staphylococcus aureus and Enterococcus faecalis exposed to daptomycin.
The novel lipopeptide antibiotic, daptomycin, at a concentration of 8 mg/L, caused gross morphological changes in both a methicillin-sensitive and a methicillin-resistant strain of Staphylococcus aureus and in a strain of Enterococcus faecalis. The earliest (after 1 h) surface lesion observed was the appearance of boss-like processes randomly distributed on the cell surface. Later, grossly deformed bacteria were seen and in two of the three bacteria prolonged exposure led to degeneration of the cells into an amorphous syncytial mass. Omission of calcium (which is known to potentiate the activity of daptomycin) from the culture medium did not affect the morphological response to an inhibitory concentration of the antibiotic.
Anti-Bacterial Agents↗
An in vitro evaluation of clavulanic acid, a potent, broad-spectrum beta-lactamase inhibitor.
The in vitro efficacy of clavulanic acid, a new broad-spectrum inhibitor of enterobacterial beta-lactamases, was investigated. In conventional agar dilution tests, the presence of a sub-inhibitory level of clavulanic acid (8 microgram/ml) lowered the minimum inhibitory concentration of ampicillin for many resistant enterobacteria to therapeutically achievable levels. When tested against dense populations of Escherichia coli and klebsiella strains in a static turbidimetric system and in an in vitro model of the treatment of bacterial cystitis, clavulanic acid plus ampicillin suppressed bacterial growth for periods far exceeding the normal interdose interval at concentrations at which neither agent alone was effective. In addition to its activity as a beta-lactamase inhibitor, clavulanic acid may interact with other beta-lactam antibiotics in a second, distinct way. Because of this synergic interactions may occur with non-beta-lactamase producing organisms, and the overall synergic effect obtained with beta-lactamase producers may be compounded of two separate elements.
Ampicillin↗