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Biomedical subjects

D Felmingham

Publications and source records attributed to D Felmingham.

At least 55 records · Page 3Linked to original sources
PubMed1994

An in vitro characterization of cefditoren, a new oral cephalosporin.

Cefditoren (ME 1206) is a new cephalosporin available for oral administration as the pivaloyloxymethyl ester (ME 1207). The effect of medium formulation. pH, cation concentration and inoculum on the in vitro activity of cefditoren was investigated prior to determining its comparative antibacterial potency against a wide range of clinical bacterial isolates, its bactericidal activity against susceptible strains and the duration of its post-antibiotic effect (PAE). Cefditoren was shown to possess a broad-spectrum of cidal antibacterial activity against both Gram-positive and Gram-negative species with stability to many beta-lactamases of clinical importance. Its activity against Gram-positive species was similar to augmentin and cefuroxime, but superior to that of cefaclor and cefixime, while its beta-lactamase stability was similar to that of cefixime and ceftazidine, characterizing it as a third generation cephalosporin. Investigation of the effect of laboratory variables on the in vitro activity of cefditoren indicates that it will present no special problems when tested in the clinical setting against bacterial pathogens. PAE of 0.9 h, or greater, for Staphylococcus spp, Streptococcus pneumoniae and Moraxella catarrhalis may support the use of an extended dose-interval when cefditoren is used for the treatment of respiratory tract infections.

Bacteria↗
PubMed1993

Audit of prescription and assay of aminoglycosides in a UK teaching hospital.

Despite potential nephrotoxicity and ototoxicity, aminoglycosides are widely used in the treatment of severe sepsis but monitoring of serum levels is necessary. The use and assay of aminoglycosides, together with microbiologists' and pharmacists' advice on dosage and potential toxicity were examined in a teaching hospital group during an eight week period. A total of 480 courses of aminoglycoside was recorded in 440 hospital in-patients and of these, 306 (64%) were for prophylaxis. For 79 (45%) of 174 therapeutic courses, bacteriological results were available at the start and the choice of antibiotic was appropriate in 69 cases. Serum aminoglycoside assays were performed in 86% (149/174) of therapeutic courses. Correct assay request forms were used in 79% of 473 assay requests, and the clinical diagnosis was given on 73% of forms. In so-called peak samples with a documented time of collection, this ranged from 5 min to over 9 h post dose. Potentially toxic concentrations were present in 56 (12%) serum samples from 50 courses, in ten of which there was a serum creatinine rise of > 40 microM. However, there were confounding factors in five cases. Probable nephrotoxicity was rare, although assays were not performed in 14% of therapeutic courses. There were no symptomatic cases of ototoxicity but audiometry and vestibular studies were not performed. Closer liaison between the microbiologists, pharmacists and clinical staff is essential to improve clinical practice. Computer notification of inadequately monitored courses would be helpful. The routine therapeutic use of aminoglycosides needs to be reviewed in the light of the rising costs of assay litigation and the increasing number of alternative antibiotics available.

Adolescent↗
PubMed1992

The early bactericidal activity of rifabutin measured by sputum viable counts in Hong Kong patients with pulmonary tuberculosis.

Previously untreated patients with smear-positive pulmonary tuberculosis were randomly allocated to treatment with 600, 300, 150 or 75 mg doses of rifabutin (LM427, ansamycin), 600, 300 or 150 mg of rifampicin, 300 mg isoniazid or to no drug daily for 2 days. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days, termed the early bactericidal activity (EBA), was estimated from counts of colony-forming units (cfu) on selective 7H-11 agar medium. The EBA for rifabutin ranged from -0.039 (an increase in counts) to 0.049 log10 cfu/ml/day whereas the EBA increased from 0.071 for 150 mg rifampicin to 0.293 log10 cfu/ml/day for 600 mg rifampicin and was 0.43 log10 cfu/ml/day for 300 mg isoniazid. The difference between the EBAs for rifabutin and rifampicin just attained significance (P = 0.05) suggesting that rifabutin was inactive or less active than rifampicin against the extracellular bacilli in pulmonary cavities. Peak plasma concentrations of rifabutin after the initial doses were found to be proportional to dose size and were approximately 7 times lower than those after the same dose size of rifampicin. The lower EBA of rifabutin as compared to rifampicin is probably due to the low plasma concentrations which are not fully compensated for by slightly greater antituberculosis activity of rifabutin in vitro.

Adolescent↗
PubMed1992

Enterococcus species in urinary tract infection.

Significant urinary isolates have been prospectively recorded since 1971. Enterococcus species, a common cause of nosocomial urinary tract infection, have been identified, and susceptibilities to a range of antibiotics have been determined. In addition, isolates in 1988 were tested for breakpoint susceptibility to vancomycin and teicoplanin. Despite changes in the hospitals covered, isolation of Enterococcus species rose steadily from 4% in 1971 to 12.6% in 1990 in hospital patients and from 2% to 5.6% in general-practice patients (P less than .01). All isolates of Enterococcus species were sensitive to ampicillin. Teicoplanin inhibited all 526 strains tested at a concentration of 2 micrograms/mL, but the same concentration of vancomycin inhibited only 370 (70%). The increased prevalence of enterococcal urinary tract infection is probably the result of increasing use of catheterization and broad-spectrum antibiotics. Glycopeptides reach high levels in the urine, and teicoplanin might be an alternative for the treatment of urinary tract infections due to enterococci.

Anti-Bacterial Agents↗
PubMed1991

The in vitro activity of some 14-, 15- and 16- membered macrolides against Staphylococcus spp., Legionella spp., Mycoplasma spp. and Ureaplasma urealyticum.

Erythromycin is a macrolide antimicrobial chemically comprised of a 14-membered lactone ring substituted with a neutral (cladinose) and an amino (desosamine) sugar. Recently, a number of new macrolide molecules have been identified containing either 14-, 15- or 16-membered substituted lactone rings. In this study the authors have determined the in vitro activity of roxithromycin and clarithromycin (both 14-membered macrolides), azithromycin (a 15-membered macrolide or azalide) and midecamycin acetate (a 16-membered macrolide) against clinical isolates of Staphylococcus spp., (including methicillin-susceptible and -resistant isolates), Legionella spp., Mycoplasma spp. and Ureaplasma urealyticum. Minimum inhibitory concentrations of the macrolides for the clinical isolates of Staphylococcus spp. examined were widely distributed. However, midecamycin acetate retained activity against those isolates of Staphylococcus spp. exhibiting inducible resistance to erythromycin and the other macrolides tested. Isolates characterised by constitutive resistance to erythromycin were also resistant to midecamycin acetate. All of the macrolides were very active against Legionella spp., with clarithromycin demonstrating the greatest potency (MIC range: less than or equal to 0.03-0.06 mg/l). Isolates of Mycoplasma pneumoniae and Ureaplasma urealyticum were susceptible to all of the macrolides tested. However, erythromycin, roxithromycin, clarithromycin and azithromycin were poorly active against isolates of Mycoplasma hominis. By contrast, the same isolates were susceptible (MIC range: 0.008-0.12 mg/l) to midecamycin acetate.

Anti-Bacterial Agents↗
PubMed1990

In-vitro studies with ramoplanin (MDL 62,198): a novel lipoglycopeptide antimicrobial.

Ramoplanin is a novel lipoglycopeptide antimicrobial complex, isolated from the fermentation products of a strain of Actinoplanes sp. (ATCC 33076), which comprises three closely related polypeptides, each containing chlorinated phenyl moieties and D-mannose. The in-vitro activity of ramoplanin was compared with those of vancomycin and teicoplanin. Ramoplanin was very active against Staphylococcus spp., irrespective of methicillin susceptibility, with all isolates inhibited by 1 mg/l or less. Concentrations of vancomycin and teicoplanin required to inhibit the same population of bacteria were 4 and 16 mg/l, respectively. Ramoplanin was also very active against Streptococcus spp. (alpha- and beta-haemolytic species, Str. pneumoniae and Enterococcus faecalis, Corynebacterium spp. (including Cory. jeikeium), Listeria monocytogenes, Gardnerella vaginalis, Propionibacterium acnes and Gram-positive anaerobic bacteria, with all isolates inhibited by 2 mg/l, or less. In general, the activity of ramoplanin against these species was either equal to or only slightly less than teicoplanin and equal to or somewhat greater than vancomycin. With the exception of Bacteroides melaninogenicus and Bact. bivius, ramoplanin was not active against Gram-negative bacteria.

Anti-Bacterial Agents↗
PubMed1990

New techniques for assessing pathogenicity of quinolone-resistant bacteria.

Ciprofloxacin and ofloxacin-resistant variants of Staphylococcus aureus and Pseudomonas aeruginosa have been compared with their original drug-sensitive progenitor strains with respect to their susceptibility to opsonophagocytosis by human polymorphonuclear leucocytes. For strains exhibiting low level resistance to each quinolone some depression of chemiluminescence (respiratory burst) was recognized whereas for strains exhibiting high level resistance some potentiation of chemiluminescence occurred. There was no difference in terms of the phagocytic ingestion of each of the strains. This study provides only limited evidence to suggest that changes in bacterial virulence are associated with the development of resistance to the quinolone antimicrobials.

Bacteriological Techniques↗
PubMed1990

In vitro activity of teicoplanin, vancomycin, A16686, clindamycin, erythromycin and fusidic acid against anaerobic bacteria.

The in vitro activity of teicoplanin and A16686, two new glycopeptide antibiotics was determined against 196 isolates of anaerobic bacteria. The activity of teicoplanin and A16686, in comparison with that of vancomycin, clindamycin, erythromycin and fusidic acid was 2 to 16 times higher against the gram positive anaerobes, namely, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Clostridium species, Peptococcus species and Peptostreptococcus species. However, Bacteroides fragilis was resistant to teicoplanin and A16686 while Bacteroides melaninogenicus and Bacteroides bivius were found to be sensitive.

Anti-Bacterial Agents↗
PubMed1990

The bactericidal activity of vancomycin and teicoplanin against Streptococcus pneumoniae.

The in vitro inhibitory and bactericidal activity of vancomycin and teicoplanin against clinical isolates of Streptococcus pneumoniae was investigated. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique. Vancomycin (MIC range 0.12-0.25 mg/l) and teicoplanin (MIC range 0.03-0.12 mg/l) were both very active against the isolates examined. Single-time-point minimum bactericidal concentrations (MBCs) were determined using a macrobroth incorporation technique. Both antimicrobials brought about a 99.9% reduction in viability of the original inocula during 24 hours' exposure at concentrations of 4-8 times the MIC for vancomycin and 2-4 times the MIC for teicoplanin. Time-kill curves of vancomycin, teicoplanin and penicillin against a penicillin-susceptible and a penicillin-resistant strain of S. pneumoniae showed a greater than 3.0 log10 cfu/ml reduction in viability of cultures within 6 hours of exposure to all three of the antimicrobials at a concentration equal to eight times the MIC. The results suggest that clinical trials of the efficacy of teicoplanin in the treatment of infections caused by S. pneumoniae are warranted.

Glycopeptides↗
PubMed1989

Serum and tissue levels of teicoplanin during cardiac surgery: the effect of a high dose regimen.

Two prospective trials suggested that teicoplanin was less effective in preventing Gram-positive wound infections after cardiac surgery than a combination of flucloxacillin and an aminoglycoside. The initial dose of 400 mg was associated with a subinhibitory concentration of teicoplanin in fat at the end of operation. In this study, the behaviour of a higher initial dose (12 mg/kg) was investigated in ten patients during coronary artery surgery. As in the earlier trials, a second dose (400 mg) was given after 24 h. The mean concentration at the end of cardiopulmonary bypass was 15 mg/l in serum, 6 mg/kg in fat and 9 mg/kg in skin, all in excess of the expected break-point for staphylococci (4 mg/l). The higher dose regimen might be more successful in surgical prophylaxis.

Adult↗