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D Felmingham

Publications and source records attributed to D Felmingham.

At least 19 recordsLinked to original sources
PubMed1996

Results of the Alexander Project: a continuing, multicenter study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens.

In 1992, an ongoing, international multicenter study was established to investigate the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens: the Alexander Project. Isolates cultured from patients living in geographically separated areas, ten in the European Union (EU) and five in the United States (US), were collected and tested using standard methods in a central laboratory. A total of 4,155 isolates of Haemophilus influenzae was collected during the period 1992-1994. beta-lactamase production was the principal mechanism of resistance observed with overall rates in the US (1992 = 26.3%; 1993 = 28.2%; and 1994 = 30.1%) generally twice those seen in the EU (1992 = 12.3%; 1993 = 14.4%; and 1994 = 15.5%). Chloramphenicol resistance was generally low except in Spanish centers where rates ranging from 4.0 to 15.9% were observed during the study period. One thousand one hundred ninety-three isolates of Moraxella catarrhalis were tested. beta-lactamase production was the only mechanism of resistance of any importance detected, with the vast majority of isolates producing the enzyme. Two thousand eight hundred twenty-nine isolates of Streptococcus pneumoniae were tested. French and Spanish centers provided isolates with the highest rates of either low-level (intermediate) or high-level penicillin resistance, which in 1994 ranged from 10.2 to 31.4% and 30.4 to 40.1% for each resistance category, respectively. With the exception of the fluoroquinolones, rates of resistance to other antimicrobials including the macrolides, doxycycline, chloramphenicol, and trimethoprim/sulfamethoxazole were high, generally, in centers with a high prevalence of penicillin resistance. However, in some centers (Toulouse, France and Genoa, Italy) this association was not complete for the macrolides.

Anti-Bacterial Agents↗
PubMed1996

A multicentre collaborative study of the antimicrobial susceptibility of community-acquired, lower respiratory tract pathogens 1992-1993: the Alexander Project.

The Alexander Project is a unique, international, collaborative antimicrobial susceptibility surveillance study of bacterial pathogens causing community-acquired lower respiratory tract infection. Fifteen centres, ten in the European Union (EU) and five in the USA, each submitted up to 400 isolated per year for 2 years (1992 and 1993) to a central laboratory for re-identification and determination of MICs of 15 antimicrobials using the Sensititre microbroth incorporation technique. Of the total of 6385 isolates collected, Haemophilus influenzae (2718), Streptococcus pneumoniae (1856) and Moraxella catarrhalis (818) were the most frequently identified pathogens. Staphylococcus aureus (690). Haemophilus parainfluenzae (183) and Klebsiella pneumoniae (120) were identified less commonly. High-level penicillin resistance in S. pneumoniae (MIC > or = 2 mg/L) was found in 222 isolates, an overall prevalence of 12% which varied from < 1% in Germany, Italy, UK and two of the five USA centres, to 3.8-40.4% in the remainder, with the highest prevalence found in France and Spain. Intermediate penicillin resistance (MIC 0.12-1 mg/L) was identified in 228 isolates of S. pneumoniae, an overall prevalence of 12.3%, with individual centre prevalence varying widely (EU, 0-52.3%; USA, 0-20.9%) and not always following that of high-level resistance. Resistance to other, unrelated, antimicrobials, except notably the fluoroquinolones, was strongly associated with beta-lactam resistance. beta-lactamase production was detected in 492 isolates of H. influenzae, an overall prevalence of 18.1%. Rates of detection varied widely between centres from 1.4% in Weingarten, Germany in 1993 to 38.5% in Barcelona, Spain in 1992. In general, the prevalence of beta-lactamase production was higher and less variable in USA centres than in those of the EU. beta-Lactamase was detected consistently in the majority of isolates of M. catarrhalis with an overall prevalence of 81.7%. Virtually no other resistance phenotype was recognised in this species. Of the 690 collected, most isolates of S. aureus produced beta-lactamase with rates of detection varying from 52.2%-89.1%. Isolates from two centres, Genoa, Italy in 1992 and Paris, France in 1993, were associated with a high prevalence of methicillin-resistance (34.8% and 43.8%, respectively). Combined isolates of H. parainfluenzae and K. pneumoniae accounted for only 4.7% of the total collection. Although the current data are insufficient to allow analysis of trends in resistance, the study participants have continued to collect further isolates in 1994 and 1995 which will be reported in the future.

Amoxicillin↗
PubMed1995

Clearance of gentamicin during cardiac surgery.

Treatment with an aminoglycoside plus flucloxacillin is commonly used to prevent wound infection and endocarditis after cardiac surgery. Cardiopulmonary bypass, blood transfusion and the lack of a steady state greatly affect handling of gentamicin. Urinary gentamicin excretion is not predictable in terms of preoperative risk factors possibly because there is no clear relationship between serum levels and gentamicin clearance. A study was performed to determine whether the existing prophylactic regimen gave adequate serum levels during surgery and to compare renal excretion of gentamicin and the trough serum levels. Ten patients received gentamicin (1.5 mg/kg at the start of surgery followed by 80 mg tds for 2 days) and flucloxacillin 500 mg qds for 2 days. Serum and urinary concentrations of gentamicin were assayed during surgery and in the early postoperative period. The median apparent serum half-life during the first 8 h was 2.5 h (95%CI 1.7-3.2 h). The median gentamicin clearance was 37 mL/min(95%CI 23-64 mL/min) and the creatinine clearance 85 mL/min (95%CI 72-210 mL/min). Serum levels remained above 1 mg/L during surgery but urinary concentrations varied between 0.4 and 364 mg/L (median 70 mg/L). At 24 h (but not 8 or 16 h), trough serum levels appeared to be related to the amount of gentamicin excreted but the relationship was not quite statistically significant (P = 0.057). Despite the effects of cardiopulmonary bypass, therapeutic serum gentamicin levels were maintained during surgery and reduced renal excretion in the postoperative period was associated with raised levels.

Cardiac Surgical Procedures↗
PubMed1995

Antibiotic prophylaxis in cardiac surgery: factors associated with potentially toxic serum concentrations of gentamicin.

Aminoglycosides are commonly used with flucloxacillin in the prevention of wound infection and endocarditis after cardiac surgery. Earlier studies suggested that the use of aminoglycosides is associated with a small but significant rise in serum creatinine. A regression analysis was performed to identify the preoperative and postoperative factors of importance in determining serum gentamicin concentrations. Serum assays might then be confined to those at particular risk of elevated serum levels. Patients received gentamicin 1.5 mg/kg at the start of surgery followed by 80 mg tds for two days in addition to flucloxacillin. Trough and peak serum gentamicin concentrations were assayed on the first and second days after surgery and urine concentrations were measured with each full catheter bag. Patient characteristics, drug therapy, operation, fluid balance and routine investigations were recorded. A total of 95 of 104 patients were evaluable. Linear discriminant analysis of factors selected by forward stepwise regression identified ten of the 15 patients with subsequent elevated gentamicin concentrations, by using age, and preoperative serum creatinine, systolic blood pressure and serum aspartate transaminase. After operation, factors such as serum creatinine, the quantity of frusemide administered in 24 h, and the integral of the systolic blood pressure over 24 h identified 12 of the 15 patients. However, no satisfactory model could predict urinary concentrations. The discriminant function using preoperative factors prospectively identified 11 of 12 patients with elevated trough levels from a total of 101 further patients. Postoperative gentamicin concentrations cannot reliably be predicted from patient characteristics. Trough assays should be performed or prophylactic courses limited to 24 h.

Adult↗
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↗