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Biomedical subjects

H A Holt

Publications and source records attributed to H A Holt.

At least 19 recordsLinked to original sources
PubMed1991

Activity of clindamycin against Staphylococcus aureus and Staphylococcus epidermidis from four UK centres.

MICs of penicillin, methicillin, clindamycin, erythromycin, sodium fusidate and gentamicin were determined by an agar dilution method for 300 current isolates of Staphylococcus aureus and 100 of S. epidermidis, collected from four centres, and 38 stock strains of methicillin-resistant S. aureus (MRSA). All but one of the 300 current isolates of S. aureus were sensitive to clindamycin (MIC less than 0.5 mg/l), with an MIC90 of 0.12 mg/l. Of a total of 39 MRSA strains, 11 (28.2%) were resistant to clindamycin (MIC greater than 32 mg/l); all of these strains were also resistant to erythromycin. Ten of the 100 strains of S. epidermidis were resistant to clindamycin; they came from a reasonably equal geographical distribution and were also resistant to erythromycin. The results suggest that clindamycin might still be useful as a second-line agent for infections caused by S. aureus and S. epidermidis, although its activity against MRSA was limited to approximately two-thirds of the MRSA strains tested in this study.

Clindamycin↗
PubMed1990

In vitro antimicrobial susceptibility of Listeria monocytogenes isolated in the UK and other Listeria species.

The MICs and MBCs of 21 antimicrobial agents were determined for 103 strains of Listeria monocytogenes isolated in the UK and 27 strains of other Listeria species. Ampicillin, penicillin, azlocillin, imipenem, gentamicin, netilmicin, amikacin, erythromycin, rifampicin, trimethoprim, clindamycin and vancomycin had good activity, while cephalothin, chloramphenicol, ciprofloxacin and ofloxacin were less active, and cefuroxime, enoxacin, norfloxacin and fosfomycin were the least active. Tetracycline had good activity against many strains, but the MIC was high for some. Unlike the other Listeria species tested, Listeria ivanovii was susceptible to fosfomycin. Inoculum size and media employed were shown to affect the MBC, tryptose phosphate broth yielding higher MBCs than Mueller-Hinton or Isosensitest broths.

4-Quinolones↗
PubMed1990

Treatment of radiation or cyclophosphamide induced hemorrhagic cystitis using conjugated estrogen.

Five patients with severe hemorrhagic cystitis induced by radiation and/or cyclophosphamide were systematically treated with conjugated estrogen. Two patients received conjugated estrogen twice each day (1 mg. per kg.) intravenously, followed on day 3 and thereafter by 5 mg. per day orally. Hematuria decreased markedly 6 to 8 hours after the initial dose and urine color became light yellow within 1 to 3 days. The other 3 patients received 5 mg. conjugated estrogen per day orally and urine color became clear within 4 to 7 days. Hematuria did not recur during 12 to 22 months in 4 patients who received daily conjugated estrogen (1.25 mg.). However, transient episodes of mild hematuria persisted in 1 patient during the 3-month followup despite a higher dose of conjugated estrogen (10 mg. per day). Complications, including thromboembolism and other side effects associated with conjugated estrogen, were not observed in these patients. We postulate that conjugated estrogen controls hematuria in hemorrhagic cystitis by decreasing the fragility of the mucosal microvasculature of the bladder.

Adult↗
PubMed1990

In-vitro synergy testing of nine antimicrobial combinations against Listeria monocytogenes.

In-vitro antimicrobial synergy against Listeria monocytogenes was assessed using nine combinations in chequerboard (bacteriostatic) tests and time-kill (bactericidal) studies. Ampicillin/gentamicin and trimethoprim/sulphamethoxazole were the most synergistic combinations in bacteristatic tests, whereas gentamicin with ampicillin, trimethoprim or vancomycin and trimethoprim/sulphamethoxazole were the most synergistic in bactericidal tests. Gentamicin-containing combinations were most effective at killing L. monocytogenes and those containing rifampicin least effective.

Anti-Bacterial Agents↗
PubMed1990

In-vitro activity of cefpodoxime against 1834 isolates from domiciliary infections at 20 UK centres.

A total of 1834 non-copy, general practice or outpatient isolates were collected by 20 hospital laboratories within the British Isles, and identified and tested for susceptibility to nine antimicrobial agents available by oral administration at one centre. Against Enterobacteriaceae cefpodoxime was the most active beta-lactam agent tested, the MIC90s being: for Escherichia coli 1.0 mg/l, for Proteus mirabilis 1.0 mg/l, for Citrobacter spp. 2.0 mg/l, and for Enterobacter spp., Serratia spp., Morganella spp. and Klebsiella spp. 16-64 mg/l. Cefpodoxime also showed a certain amount of activity against staphylococci and high activity against streptococci, the MIC90s being for Staphylococcus aureus 2 mg/l, for coagulase negative staphylococci 8 mg/l, for Streptococcus pyogenes 0.015 mg/l, for Str. pneumoniae 0.06 mg/l and for Str. agalactiae 0.5 mg/l.

Ceftizoxime↗
PubMed1989

A problem encountered using staphylococcus/streptococcus supplement.

A problem was encountered while using a commercial staphylococcus/streptococcus selective supplement in blood agar culture medium. A number of strains of Staphylococcus aureus failed to grow, although they grew well on non-selective media. The phenomenon was shown to be a result of a pH change caused by incubation in a carbon dioxide-enriched atmosphere, potentiating the activity of the nalidixic acid component. It is recommended that media containing this supplement are not incubated in CO2 enriched atmospheres.

Anti-Bacterial Agents↗
PubMed1988

The in-vitro degradation at 37 degrees C of vancomycin in serum, CAPD fluid and phosphate-buffered saline.

Solutions of vancomycin in phosphate-buffered saline, peritoneal dialysis effluent fluid and human serum were incubated at 37 degrees C for ten days and sampled at daily intervals. The samples were assayed for vancomycin content by a microbiological assay, HPLC and polarisation fluoroimmunoassay (Abbott TDX). The results obtained by HPLC and microbiological assay agreed well and indicated approximately 50% loss over ten days in serum and buffered saline and over 70% loss in dialysate. TDX results indicated losses of only 20% and 40%, respectively. Degradation products were prepared from vancomycin by acid hydrolysis and purified by HPLC. These purified products were shown to cross-react in the TDX assay. It is suggested that the TDX assay becomes non-specific in the presence of vancomycin breakdown products and thus overestimates true vancomycin concentrations.

Bacteriological Techniques↗
PubMed1988

Resistance of bacterial pathogens to four aminoglycosides and six other antibacterials and prevalence of aminoglycoside modifying enzymes, in 20 UK centres.

A total of 5116 non-fastidious bacterial strains isolated from either blood or urine culture were collected from 20 geographically distributed centres within the UK. Upon receipt the strains were identified and the minimum inhibitory concentrations of ten antimicrobial agents in hospital usage were determined for each of the strains. All laboratories submitted a similar range of bacterial species and in species normally considered as sensitive the overall rates of resistance to the different antibiotics tested were: amikacin 2.4%, gentamicin 3.7%, netilmicin 2.6%, tobramycin 3.4%, ampicillin 41.7%, cefadroxil 11.6%, cefotaxime 1.4% [corrected], cefuroxime 4.3%, ciprofloxacin 0.6% and trimethoprim 13.0%. For those strains resistant to one or more aminoglycosides the mechanisms of resistance responsible were determined from the aminoglycoside-resistance patterns of the strains to 16 different aminoglycoside antibiotics. The predominant mechanisms of resistance found were APH(2") + AAC(6') production in staphylococci. AAC(2') production in Providencia spp., and AAC(3) production in the other Gram-negative genera.

Aminoglycosides↗
PubMed1987

Activity in vitro of CGP 31608, a new penem antibacterial agent.

The in-vitro activity of CGP 31608 (hereinafter termed CGP), a new penem, was tested by an agar dilution technique in comparison with imipenem, Sch 34343, cefotaxime, ceftazidime, aztreonam, ampicillin, gentamicin and ciprofloxacin. 480 clinical isolated were tested, some of which were selected because of their multiple resistance. CGP showed consistent activity against a wide range of species, having MIC90 values of 2-8 mg/l for almost all Enterobacteriaceae, Pseudomonas spp., Haemophilus spp., Corynebacterium spp. and Bacteroides spp. It was the most active agent tested against staphylococci having an MIC90 of 0.25 mg/l, showing no reduction in activity against methicillin-resistant strains. Lesser activity was observed against some streptococci, Proteus spp. and clostridia. Tests carried out in broth demonstrated that CGP activity was constant over a pH range of 6-8 and was unaffected by the presence of 50% serum or 50% urine. The rate of killing of CGP, gentamicin, cefotaxime and ciprofloxacin was investigated in broth against log and stationary-phase cultures of Staphylococcus aureus and Escherichia coli. The most rapid rate of kill was seen with ciprofloxacin, while CGP exhibited a more rapid bactericidal effect than cefotaxime against Staph. aureus. The stability of CGP was studied at two concentrations in serum, broth and phosphate buffer at 4 degrees C, room temperature and 37 degrees C. In serum the half-life was 112 h at 4 degrees C, 35 h at room temperature and 11.4 h at 37 degrees C. Protein binding tested at concentrations of 5-100 mg/l was 2-6.3%.

Anti-Bacterial Agents↗
PubMed1986

Effect of oral ciprofloxacin on the faecal flora of healthy volunteers.

The effect of oral ciprofloxacin on the intestinal flora was investigated in six male volunteers aged between 21 and 54 years. Faecal specimens were cultured quantitatively for aerobic and anaerobic micro-organisms before, during and after a five day course of ciprofloxacin. Ciprofloxacin resulted in a significant reduction in aerobic flora in all volunteers and colonisation with resistant coagulase-negative staphylococci or corynebacteria in two volunteers. The total anaerobic flora counts were significantly reduced in only one volunteer. Neither Clostridium difficile nor its toxin was detected and there was no significant colonisation with Pseudomonas spp. or yeasts; no ciprofloxacin-resistant gram-negative bacilli were detected. Peak serum levels on days 1 and 5 of 1.6-4.3 mg/l (mean 2.7) were achieved after 30-90 min and urine recovery over the five days was 27.1-44.6%.

Administration, Oral↗
PubMed1986

Pharmacokinetics of cefotetan in patients with end-stage renal failure on maintenance dialysis.

The pharmacokinetics of a single intravenous dose of cefotetan were studied in 17 volunteer patients with end-stage renal failure, requiring intermittent haemodialysis in 12 cases or undergoing continuous ambulatory peritoneal dialysis in 5 cases. Between haemodialysis the mean plasma elimination half life was 20.4 h (S.E.M. +/- 2.1). This decreased to 7.5 h (S.E.M. +/- 0.6) during haemodialysis. In patients treated by continuous ambulatory peritoneal dialysis the mean plasma elimination half life was 15.5 h (S.E.M. +/- 1.9). Small amounts of cefotetan (5-9% of the administered dose) were recovered in the peritoneal dialysates removed over the 24 h following the dose.

Cefotetan↗
PubMed1985

The human pharmacokinetics of cefotaxime and its metabolites and the role of renal tubular secretion on their elimination.

The pharmacokinetics of cefotaxime were investigated in human volunteers given constant intravenous infusions, intravenous bolus, and intramuscular doses of the drug. After intravenous dosing, the plasma levels of cefotaxime declined in a biphasic manner with a terminal half-life varying between 0.92 and 1.65 hr. Moreover, the pharmacokinetics were linear up to at least a 2.0 g dose for volume of distribution based on area (23.3-31.3 l), plasma clearance (249-2.88 ml/min), and renal clearance (151-177 ml/min). Renal tubular secretion of intact cefotaxime and each of its metabolites was demonstrated by its interaction with probenecid, although the ratio of drug to metabolites ultimately excreted in urine after probenecid was similar to that seen normally (54 +/- 6, 19 +/- 4, 6.5 +/- 0.7 and 5.5 +/- 0.7% for cefotaxime, DACM, M2, and M3, respectively, when calculated as a percentage of the dose). The observed half-lives of DACM, M2, and M3 were 2.3 +/- 0.4, 2.2 +/- 0.1 and 2.2 hr, respectively. However, when the true half-life of DACM was calculated (0.83 +/- 0.23 hr) it was not only significantly shorter than that observed but also shorter than that for intact cefotaxime. The plasma clearance of DACM (744 +/- 226 ml/min) was much higher than that of cefotaxime while the volume of distribution was of a similar order (56 +/- 24 l). When administered intramuscularly, there was good absorption of cefotaxime from the site of injection (92-94%) giving maximum plasma levels of the drug of between 30 and 35 mg/l at approximately 40 min after dosing. Thereafter, the plasma levels of cefotaxime declined in a monophasic manner with a half-life (1.0-1.2 hr) similar to that of the terminal half-life seen after intravenous administration. Lidocaine had no significant effect on either its absorption or elimination kinetics.

Adult↗