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Biomedical subjects

H A Holt

Publications and source records attributed to H A Holt.

At least 73 records · Page 4Linked to original sources

The in vitro antibacterial activity of ceftriaxone in comparison with nine other antibiotics.

The results of a large three centre co-ordinated study into the in vitro susceptibility of bacterial clinical pathogens showed no significant evidence of regional variation within the U.K. towards the 10 antibiotics examined. The newer cephalosporins were highly potent and superior to other antibiotics against the Enterobacteriaceae, with ceftriaxone and cefotaxime the most potent. Against Pseudomonas aeruginosa, gentamicin was the most active, followed by ceftazidime, piperacillin and ceftriaxone; cefotetan was the least active. Staphylococcus aureus and Staphylococcus albus were most susceptible to cefuroxime and gentamicin, though most were also susceptible to ceftriaxone, cefotaxime and cefoxitin. Streptococcus (Groups A and B), Streptococcus pneumoniae and Neisseria spp. were susceptible to most agents other than gentamicin, but ceftriaxone and cefotaxime were overall the most potent. Ceftriaxone was the most active agent against Haemophilus influenzae. The newer agents were variable and relatively poor against anaerobes and only amoxycillin and piperacillin were significantly active against Streptococcus faecalis. The overall resistance level to the third generation cephalosporins was low.

Anti-Bacterial Agents↗

In-vitro studies with ciprofloxacin, a new 4-quinolone compound.

Ciprofloxacin is a new antibacterial agent of the 4-quinolone group. With an agar dilution technique we compared its activity on 365 clinical isolates with those of norfloxacin, nalidixic acid, ampicillin, mezlocillin, cefadroxil, cefuroxime, ceftazidime, ceftriazone , cefotaxime, latamoxef (moxalactam), and gentamicin. Ciprofloxacin was overall the most active agent tested against aerobic Gram-negative species, with the MIC90 values for all species being below 1 mg/l (excepting Providencia stuartii with 4 mg/l), and the large majority being below 0.12 mg/l. Many of the strains were selected on the basis of resistance to beta-lactam agents or gentamicin, and ciprofloxacin was also active against these. There was little difference in the activity of ciprofloxacin at inocula of 10(4) or 10(6) cfu. Strains with higher MIC's of the related agents norfloxacin and nalidixic acid were less susceptible to ciprofloxacin . Ciprofloxacin was less active against Gram-positive species (typical MIC90 values were 0.5 or 1 mg/l) and obligate anaerobes (4 mg/l for Bacteroides fragilis). The activity of ciprofloxacin in broth dilution tests was little affected by pH over the range 6.0-8.0, or by human serum or tissue fluid; its activity was reduced by the presence of urine. Binding to human serum protein was 20-28%. Ciprofloxacin was rapidly bacterial in broth at concentrations near to its MICs. By exposure to subinhibitory concentrations of ciprofloxacin it was possible to increase its MIC for bacteria in daily subcultures. The final MIC values after ten days were often about 16-fold greater than those observed initially.

Anti-Bacterial Agents↗

The activity of enoxacin against clinical bacterial isolates in comparison with that of five other agents, and factors affecting that activity.

The activity of enoxacin against 362 clinical bacterial isolates in comparison with norfloxacin, nalidixic acid, ampicillin, latamoxef (moxalactam) and gentamicin was tested by an agar dilution method. Typical MICs for enterobacteria lay between 0.12 and 1.0 mg/l. Enterobacter spp. and Serratia spp. tended to be more resistant. Enoxacin was also active against Pseudomonas aeruginosa (mean MIC 0.5 mg/l) and highly active against fastidious Gram-negative aerobes. Typical MICs for Staphylococcus aureus were 1-2 mg/l while streptococci were more resistant (16-32 mg/l). Enoxacin had no useful activity against Bacteroides fragilis and Clostridium perfringens. Enoxacin was generally more active at pH 8 than pH 6, and in broth than in urine. It was bactericidal in its action. Daily serial passage from growth in broth containing enoxacin caused decreased sensitivity which was limited to four- to 16-fold greater than the original MIC. Enoxacin was about half as active as norfloxacin against enterobacteria, equally active against staphylococci, and some two to four times less active against streptococci.

Bacteria↗

Cefaclor and amoxycillin in the treatment of infective exacerbations of chronic bronchitis.

The clinical effectiveness of cefaclor 500 mg three times daily in the treatment of acute infective exacerbations of chronic bronchitis has been investigated by a double-blind comparison with amoxycillin in the same dose in 30 in-patients and 50 out-patients. The two antibiotics were equally effective, in terms of resolution of presenting symptoms, sputum conversion and fall in 24 h sputum weight. Side effects were infrequent. Serum and sputum concentrations of antibiotics and 24 h urinary recovery were measured in 27 patients. Concentration of both cefaclor and amoxycillin was found to be significantly lower in mucoid sputum than in purulent sputum, in contrast to earlier reports in the case of amoxycillin. No clinical advantage was apparent for patients achieving higher sputum concentration of either antibiotic.

Aged↗

The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers.

1 Cefoxitin was given by acute intravenous injection to six healthy volunteers, in a crossover study to investigate the effects of concurrent probenecid administration. 2 Serum antibiotic concentrations were determined by microbiological assay. Cefoxitin concentrations were simultaneously determined in the fluid of blisters produced by topical cantharides. All antibiotic was accounted for in the urine. 3 Cefoxitin was administered by intravenous infusion, subsequent to a loading dose, to produce steady state levels in the region of 10 microgram/ml, in one volunteer. The procedure was later repeated after prior administration of probenecid in the same subject. 4 Pharmacokinetic analyses indicated significant changes only in the parameters associated with renal excretion of drugs. Clearance was reduced by half. 5 The absolute and relative amounts of antibiotic in the central and peripheral compartments were calculated for both modes of administration. In the acute study probenecid produced a small change in distribution away from the peripheral or tissue compartment, towards the central compartment. 6 There was no elevation of initial serum concentrations and sustained levels of antibiotic could be accounted for principally by retarded excretion produced by probenecid, with little contribution by alteration in the disposition of antibiotic. 7 The sustained serum levels of cefoxitin that resulted from its decreased excretion were also reflected in blister fluid. It was concluded that the sustained cefoxitin levels produced by probenecid resulted in similar raised levels in the peripheral or "tissue' compartment, since the redistribution away from the peripheral compartment did not contribute materially to other changes in disposition of drug.

Adult↗

Bactericidal or bacteristatic effects of two sulphonamide plus trimethoprim preparations in human urine.

Rrine collections were made by ten volunteers taking cotrimoxazole and a sulphamoxole/trimethoprim combination on a cross-over basis. The latter was given in approximately half the dose of cotrimoxazole. Following collection of urine and its sterile filtration, the trimethoprim and sulphonamide concentrations were estimated. The urines were then inoculated with various species of Enterobacteriaceae whose minimum inhibitory concentrations had been previously determined. The viable counts in these urines were followed for 24 hours and from these the times to kill 90% of bacteria were calculated. These were very reproducible for any one experiment but showed no correlation with drug concentration, source of the urine or organism sensitivity, except for one organism which had high resistance to both sulphonamide and trimethoprim. When the organism was sensitive to at least trimethoprim a slow bactericidal effect was generally seen with either combination. We concluded that in this type of experiment the higher dosed combination showed no advantage contrary to a previous report, but in agreement with another. This brings into question the current dosage regime of cotrimoxazole when used to treat urinary tract infections in that its higher dosage over certain other sulphonamide/trimethoprim combinations appears to confer no advantage in our experiments.

Bacteriuria↗