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Biomedical subjects

B Slocombe

Publications and source records attributed to B Slocombe.

30 records · Page 2Linked to original sources
PubMed1985

Bactericidal effects of amoxycillin/clavulanic acid and ticarcillin/clavulanic acid in in-vitro kinetic models.

The bactericidal effects of amoxycillin and ticarcillin in the presence of clavulanic acid against beta-lactamase-producing bacteria were investigated in in-vitro kinetic models. Amoxycillin/clavulanic acid was rapidly bactericidal as a simulated intravenous 1.2 g bolus dose, against a strain of Klebsiella pneumoniae highly resistant to amoxycillin. Similarly, ticarcillin/clavulanic acid at concentrations similar to those achieved with a 30 min iv infusion of ticarcillin/clavulanic acid (5.0 g/200 mg) produced bactericidal effects against a ticarcillin-resistant strain of Pseudomonas aeruginosa. Addition of gentamicin to the system resulted in a further enhancement of activity.

Amoxicillin↗
PubMed1985

Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use.

Mupirocin (pseudomonic acid A), an antibiotic produced by Pseudomonas fluorescens, showed a high level of activity against staphylococci and streptococci and against certain gram-negative bacteria, including Haemophilus influenzae and Neisseria gonorrhoeae, but was much less active against most gram-negative bacilli an anaerobes. Nearly all clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis, including multiply resistant strains, were susceptible (mupirocin MIC, less than or equal to 0.5 microgram/ml). There was no cross-resistance between mupirocin and clinically available antibiotics, and the selection of resistant variants in vitro occurred at a low frequency. Mupirocin was highly bound (95% bound) to the protein of human serum, and activity was reduced 10- to 20-fold in the presence of human serum. The activity of mupirocin was not greatly influenced by inoculum size but was significantly enhanced in acid medium. In tests of bactericidal activity, MBCs were 8- to 32-fold higher than MICs and the antibiotic demonstrated a slow bactericidal action in time-kill tests, resulting in 90 to 99% killing after 24 h at 37 degrees C.

Anti-Bacterial Agents↗
PubMed1985

Temocillin. In vitro antibacterial activity.

Temocillin, a 6-alpha-methoxy penicillin derivative, was tested in vitro against 516 recent clinical isolates of Enterobacteriaceae. The compound exhibited good antibacterial activity, with 95% of isolates inhibited by a range 2 to 16 mg/L. Further studies, against selected isolates resistant to ticarcillin, piperacillin and cefuroxime (Klebsiella oxytoca, 25; Enterobacter species, 34; and Citrobacter species, 5), showed about half of the isolates of K. oxytoca (11/25) to be resistant to aztreonam (MIC range 16-greater than or equal to 128 mg/L), but susceptible to temocillin, cefotaxime and latamoxef. In general, the resistant strains of Enterobacter species tested were not susceptible to cefotaxime (MIC range 16-128 mg/L), or aztreonam (MIC range 1.0-64 mg/L), and many exhibited reduced susceptibility to latamoxef (MIC range 2-128 mg/L). In contrast, all the strains were susceptible to temocillin (MIC range 4-16 mg/L). The bactericidal activity of temocillin was confirmed against selected aztreonam-resistant strains of K. oxytoca and Enterobacter cloacae by conventional time-kill studies, and against a strain of E. cloacae in an in vitro model system designed to simulate the temocillin concentration profiles attained in extravascular fluid such as peripheral lymph. In the time-kill studies, temocillin concentrations of 16 and 32 mg/L were shown to effectively reduce the numbers of viable bacteria by 99 and 99.9%, respectively, within 12 hours. In the in vitro model system the numbers of bacteria were reduced 99.9% over the initial 4-hour period. In combination with aminoglycoside antibiotics, temocillin exerted a synergistic or partially synergistic effect (sigma FIC less than or equal to 0.75) against the majority of strains of Pseudomonas aeruginosa tested. When combined with piperacillin, cefotaxime or latamoxef, temocillin, unlike cefoxitin, exhibited no antagonism against strains of Enterobacteriaceae producing inducible cephalosporinases.

Anti-Bacterial Agents↗
PubMed1985

Human pharmacokinetics and antimicrobial activities of the temocillin epimers.

The pharmacokinetics of the epimers of temocillin were investigated in 4 healthy male subjects following intravenous administration of 1g of temocillin disodium (free acid) which contains a R : S epimer ratio of approximately 65 : 35. The R epimer had a 2-fold greater total plasma clearance, a 23% larger volume of distribution and a shorter beta half-life than the S epimer. Intermediate values were obtained for total temocillin (R + S) from high pressure liquid chromatography (HPLC) data. In each plasma sample, the unbound fraction of the R epimer was generally 2-fold higher than that of the S epimer, which is suggested as the reason for the differences in the pharmacokinetic properties of the epimers. The temocillin pharmacokinetic parameters obtained from the microbiological assay data reflect most closely those for the R epimer derived from HPLC data. The resolved R epimer exhibited twice the potency of the S epimer against the microbiological assay organism Pseudomonas aeruginosa NCTC 10701. However, in tests for antibacterial susceptibility, for instance minimum inhibitory concentration (MIC) determinations involving prolonged incubation, there was little difference in the inhibitory activities of the resolved R and S epimers compared with temocillin (R + S), presumably as a consequence of the epimerization of the individual epimers. In contrast, in rapid tests for bactericidal activity, which minimise the effect of epimerization, the R epimer exhibited greater bactericidal activity than the S epimer.

Adult↗
PubMed1984

In vitro antibacterial properties of BRL 36650, a novel 6 alpha-substituted penicillin.

BRL 36650 is a new type of penicillin in which a formamido group has been introduced into the 6 alpha-position of the nucleus. The compound is highly active against aerobic gram-negative bacteria and is stable to a wide range of beta-lactamases produced by these organisms. Against members of the family Enterobacteriaceae, BRL 36650 was considerably more active than piperacillin, particularly against beta-lactamase-producing strains, and showed a similar level of activity to moxalactam, aztreonam, and the third-generation cephalosporins cefotaxime and ceftazidime. Against Pseudomonas aeruginosa and other Pseudomonas species, BRL 36650 was more active than piperacillin, cefoperazone, and aztreonam and compared favorably with ceftazidime. BRL 36650 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains, and against Acinetobacter calcoaceticus. Clinical isolates of Enterobacter species and P. aeruginosa which showed markedly reduced susceptibility to cefotaxime, ceftazidime, and aztreonam were only slightly less susceptible to BRL 36650. Against Bacteroides fragilis and most gram-positive bacteria, BRL 36650 showed only a low level of activity. BRL 36650 was found to be only 35% bound to human serum protein, and the antibacterial activity was little affected by the presence of serum. In contrast, the composition of the test medium influenced the activity of BRL 36650 slightly, and an antagonistic effect could be demonstrated between the compound and a component of certain Mueller-Hinton media.

Anti-Bacterial Agents↗
PubMed1981

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans.

BRL 17421 is a new semisynthetic beta-lactam antibiotic with an unusual spectrum of antibacterial activity. The compound exhibits exceptional stability to a wide range of bacterial beta-lactamases and is active against the majority of Enterobacteriaceae, including strains highly resistant to many of the penicillins and cephalosporins currently available. Among the clinical isolates of Enterobacteriaceae tested, the frequency of strains resistant to BRL 17421 was found to be low, and there was a slow rate of emergence of resistance during in vitro studies. BRL 17421 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains. The compound was markedly less active against Pseudomonas aeruginosa and Bacteroides fragilis than against the Enterobacteriaceae. Against the gram-positive bacteria, BRL 17421 showed a very low level of activity. BRL 17421 was found to be 85% bound to human serum, and the antibacterial activity was diminished two- to fourfold in the presence of human serum. Against experimental infections in mice, the activity of BRL 17421 reflected the properties observed in vitro. Studies in human volunteers showed unusually high and prolonged serum concentrations of the compound after parenteral dosage, with a serum half-life of about 5 h, and approximately 85% of the dose was recovered unchanged in the urine. BRL 17421 was poorly absorbed after oral administration. The compound was well tolerated after intramuscular and intravenous administration in volunteers, with no adverse side effects.

Animals↗
PubMed1977

Aminoglycoside-resistant enterococci.

Thirty-four recent clinical isolates of Streptococcus faecalis were tested for sensitivity to amoxycillin, benzylpenicillin, streptomycin, kanamycin, gentamicin, tobramycin, and amikacin. Amoxycillin was two- to four-fold more active than benzylpenicillin and all strains were inhibited by low concentrations of the penicillins. The aminoglycosides were less active against the enterococci than were the penicillins and a significant number of strains were insensitive or relatively insensitive to one or more of the aminoglycosides. Thus, eight (23%) strains showed a high level of resistance to streptomycin and kanamycin (MIC greater 5000 microng/ml) but were sensitive to gentamicin, tobramycin, and amikacin. In addition, two strains of Strep. faecalis, isolated at different hospitals from patients who had received topical gentamicin therapy, were relatively resistant to gentamicin (MIC250 to 500 microng/ml) and were less sensitive also to the other aminoglycosides. Bactericidal synergy was demonstrated by amoxycillin/aminoglycoside combinations against the enterococci, provided that the test strain of Strep. faecalis was sensitive to the aminoglycoside in the combination. An exception to this was the combination of amoxycillin plus amikacin which was not synergistic against kanamycin-resistant strains of Strep. faecalis although these organisms were sensitive to amikacin in the growth inhibition tests. The gentamicin-resistant strains showed variable responses to amoxycillin/aminoglycoside combinations in tests for bactericidal synergy and were generally less sensitive than typical strains of Strep. faecalis.

Aminoglycosides↗
PubMed1977

A double trial of amoxycillin in the treatment of gonorrhoea.

A double blind comparison of two regimens of amoxycillin plus probenecid in the treatment of uncomplicated anogenital gonorrhoea is reported. Forty-three (86-0%) of 50 patients treated with 1 g amoxycillin plus 1 g probenecid and followed-up for 14 days were regarded as cured, and 51 (94-4%) of 54 patients treated with 3 g amoxycillin plus 1 g probenecid were regarded as cured. Fifty-nine per cent of 69 isolates of Neisseria gonorrhoeae were sensitive to amoxycillin (minimum inhibitory concentration less than or equal to 0-05 mg/ml). Although there was no statistical difference between the results of the two regimens it is concluded that the larger dose of amoxycillin plus probenecid is required where only 60% of gonococci are sensitive to amoxycillin.

Amoxicillin↗
PubMed1973

Transferable antibiotic resistance in enteropathogenic Escherichia coli between 1948 and 1968.

Enteropathogenic strains of Escherichia coli which had been isolated in the United Kingdom during three periods between 1948 and 1968, namely 1948 to 1951, 1957 to 1960, and 1967 to 1968, were tested for susceptibility to ampicillin, streptomycin, tetracycline, chloramphenicol, and sulphonamides. Antibiotic-resistant strains were tested for their ability to transfer antibiotic resistance to an antibiotic-susceptible strain of E. coli K-12. A relatively high proportion of strains isolated between 1948 and 1951 was resistant to ampicillin, streptomycin, or sulphonamides. None of these strains transferred ampicillin or streptomycin resistance, but sulphonamide resistance was R-factor-mediated in three out of 14 sulphonamide-resistant strains. Resistance to tetracycline and chloramphenicol was rare before 1951 but had become common among enteropathogenic E. coli by 1957. Much of the antibiotic resistance of bacteria isolated between 1957 and 1960 was R-factor-mediated, and transferable resistance was about as prevalent among E. coli isolated between 1957 and 1960 as among strains isolated in 1967 and 1968. Nevertheless, there was no appreciable increase in the overall incidence of antibiotic resistance among these enteropathogenic strains of E. coli between 1957 and 1968, although transferable antibiotic resistance was common during this period. These results do not suggest that the emergence of transferable antibiotic resistance will inevitably lead to the rapid development of antibiotic resistance among this group of bacteria.

Anti-Bacterial Agents↗
PubMed1969

Sensitivity of Gram-negative bacilli to ampicillin after six years' clinical use.

A total of 1,102 clinical isolates of Gram-negative bacilli was obtained from four hospitals during 1967 and these cultures were tested for sensitivity to ampicillin. Approximately 80% of the strains of Escherichia coli and 90% of the strains of Proteus mirabilis, the two organisms most frequently isolated, were sensitive to ampicillin. Klebsiella-Enterobacter species and Pseudomonas aeruginosa were generally insensitive. Comparison of these results with data obtained in an earlier study with Gram-negative organisms isolated in 1961 showed that there had been no significant increase in the incidence of resistance of Gram-negative bacilli to ampicillin during the period 1961-67. The majority of ampicillin-resistant strains of E. coli isolated in 1967 transferred ampicillin resistance to a sensitive strain of E. coli K12. Only four ampicillin-resistant strains of E. coli isolated in 1961 were available for transferable resistance tests but all four strains transferred ampicillin resistance. Infective or transferable resistance was therefore a feature of ampicillin resistance of certain Gram-negative bacteria before ampicillin became generally available for clinical use.

Ampicillin↗