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D Felmingham

Publications and source records attributed to D Felmingham.

At least 37 records · Page 2Linked to original sources
PubMed2001

Microbiological profile of telithromycin, the first ketolide antimicrobial.

Telithromycin, the first of the ketolide antimicrobials, has been specifically designed to provide potent activity against common and atypical/intracellular or cell-associated respiratory pathogens, including those that are resistant to beta-lactams and/or macrolide-lincosamide-streptograminB (MLS(B)) antimicrobials. Against gram-positive cocci, telithromycin possesses more potent activity in vitro and in vivo than the macrolides clarithromycin and azithromycin. It retains its activity against erm-(MLS(B)) or mef-mediated macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes and against Staphylococcus aureus resistant to macrolides through inducible MLS(B) mechanisms. Telithromycin also possesses high activity against the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis, regardless of beta-lactamase production. In vitro, it shows similar activity to azithromycin against H. influenzae, while in vivo its activity against H. influenzae is higher than that of azithromycin. Telithromycin's spectrum of activity also extends to the atypical, intracellular and cell-associated pathogens Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae. In vitro, telithromycin does not induce MLS(B) resistance and it shows low potential to select for resistance or cross-resistance to other antimicrobials. These characteristics indicate that telithromycin will have an important clinical role in the empirical treatment of community-acquired respiratory tract infections.

Anti-Bacterial Agents↗
PubMed2000

The Alexander Project 1996-1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections.

The Alexander Project was established in 1992 to examine antimicrobial susceptibilities of bacterial isolates from community-acquired infections of the lower respiratory tract. Testing of a range of compounds was undertaken in a central laboratory. From 1992 to 1995, isolates were collected from geographically separated areas in countries in the European Union and various states in the USA. In 1996, the study was extended to include centres in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not included previously. Data generated by the project during 1996-1997 confirm France and Spain as European centres with high rates of resistance to penicillin among isolates of Streptococcus pneumoniae. Both intermediate (MIC 0. 12-1 mg/L) and resistant (MIC 2 mg/L) phenotypes are present. Combined resistance rates (intermediate and resistant) were >/=50% in 1997. Combined resistance rates in excess of 20% were found in the Republic of Ireland, Portugal, the Slovak Republic and Hungary. Penicillin resistance continues to evolve in the USA, with combined resistance rates of 16.4% (1996) and 18.6% (1997). In the new, non-European centres, e.g. Mexico and, in particular, Hong Kong (where resistant strains accounted for 50% of all isolates of S. pneumoniae in 1996 and 55.5% in 1997), there are centres where rates of resistance are high. Macrolide resistance is increasing generally among both penicillin-resistant and penicillin-susceptible isolates of S. pneumoniae. There is variation between countries, and in four out of the 16 centres for which both 1996 and 1997 data are available, rates of macrolide resistance have fallen. Overall, the percentage of S. pneumoniae strains that is resistant to macrolides exceeds the percentage that is resistant to penicillin. In 1996, 16. 5% of all S. pneumoniae isolates were resistant to macrolides compared with 10.4% resistant to penicillin, and in 1997 respective rates were 21.9% and 14.1%. beta-Lactamase production was the principal mechanism of resistance observed among isolates of Haemophilus influenzae. However, considerable variation in the percentage of isolates producing beta-lactamase (0-37.1%) was observed within this species. Within Europe, in the Republic of Ireland, France and Belgium, more than 15% of isolates were beta-lactamase producers. In Spain rates were as high as 31.7%. Outside Europe and the USA high rates were described in Mexico (25%), Saudi Arabia (27.9%, 16.7%) and Hong Kong (37.1%, 28.9%). Of H. influenzae from the USA, 30.4% were beta-lactamase producers in 1996 and 23.3% in 1997. beta-Lactamase production among isolates of Moraxella catarrhalis was observed in >90% of the isolates tested in 1996 and 1997.

Anti-Bacterial Agents↗
PubMed2000

Respiratory pathogens: assessing resistance patterns in Europe and the potential role of grepafloxacin as treatment of patients with infections caused by these organisms.

Although most respiratory tract infections (RTI) are caused by viruses, various bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, are common causes of community-acquired pneumonia, acute exacerbations of chronic bronchitis, otitis media and sinusitis. Empirical antibiotic therapy of patients with RTI must take account of the increasing prevalence of resistance among the predominant pathogens. Europe-wide susceptibility surveillance studies have revealed that resistance to penicillin and macrolides is highly prevalent among isolates of S. pneumoniae from France and Spain. Uniquely, in Italy, macrolide resistance is highly prevalent while the prevalence of penicillin resistance is low. Resistance to other antibiotic classes, including chloramphenicol, doxycycline and, in particular, co-trimoxazole, is associated with penicillin resistance in pneumococci, but resistance to the fluoroquinolones is rare. beta-Lactamase production is the principal mechanism of resistance in isolates of H. influenzae and M. catarrhalis, with fluoroquinolone resistance being detected rarely in these pathogens. In 1998 a surveillance study involving 15 European countries determined the susceptibilities of many respiratory pathogens to a range of antimicrobials, including grepafloxacin. The MIC(90) of grepafloxacin for 1251 isolates of S. pneumoniae was 0.25 mg/L, the MICs for only five strains being >2 mg/L, and 99.4% of all of the isolates tested were inhibited by concentrations </=0.5 mg/L. The MIC(90)s of grepafloxacin for 587 isolates of H. influenzae and 323 of Haemophilus parainfluenzae were 0.015 and 0.06 mg/L, respectively, while that for 509 isolates of M. catarrhalis was 0.03 mg/L. The MIC(90)s for 1164 isolates of methicillin-susceptible Staphylococcus aureus and 435 isolates of Klebsiella pneumoniae were 0.12 and 0.25 mg/L, respectively. Other studies have shown grepafloxacin to be highly active against clinical isolates of Legionella pneumophila (MIC(90) 0.015 mg/L), Mycoplasma pneumoniae (MIC(90) 0.5 mg/L) and Chlamydia pneumoniae (MICs 0.06-0.12 mg/L). Current susceptibility data indicate that fluoroquinolone resistance rates among bacterial respiratory tract pathogens are low in European countries. The enhanced potency and activity of grepafloxacin against isolates of S. pneumoniae, including those exhibiting resistance to unrelated classes of antibiotics, together with its activity against other respiratory tract pathogens, suggest that this drug has considerable potential as empirical therapy of patients with a wide range of RTI.

Anti-Infective Agents↗
PubMed1999

Differences between the activity of penicillin, amoxycillin, and co-amoxyclav against 5,252 Streptococcus pneumoniae isolates tested in the Alexander Project 1992-1996.

A number of published studies have shown that the MICs of amoxycillin and/or co-amoxyclav are lower than those of ampicillin and/or penicillin for Streptococcus pneumoniae. Other published studies have concluded that the activities of amoxycillin and co-amoxyclav are comparable with that of penicillin for S. pneumoniae. A collection of 5252 S. pneumoniae isolates obtained during a 5 year period (1992-1996) was analysed to determine differences between the MICs of penicillin, amoxycillin and co-amoxyclav. Among the isolates analysed, 3788 (72%) were penicillin-susceptible, 615 (12%) were penicillin-intermediate and 849 (16%) were penicillin-resistant. Differences between the agents were assessed by examination of MIC distribution functions and simultaneous 95% CIs. In addition, penicillin-intermediate and -resistant isolates were analysed to determine the number and percentage of isolates which had an amoxycillin and co-amoxyclav MIC less than, equal to, or greater than the penicillin MIC. Results showed that the amoxycillin and co-amoxyclav MIC90s were one two-fold dilution lower than those of penicillin for all isolates collected between 1992-1993 and 1994-1996. Simultaneous 95% CIs showed that the mean differences between MICs of amoxycillin and penicillin, and between MICs of co-amoxyclav and penicillin, were less than zero. The majority of the penicillin-intermediate and penicillin-resistant isolates had an amoxycillin and co-amoxyclav MIC less than the penicillin MIC. In conclusion, amoxycillin and co-amoxyclav MICs were shown to be lower than the penicillin MICs for the S. pneumoniae isolates analysed in this study.

Amoxicillin↗
PubMed1999

Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogens--findings of the Alexander Project 1992-1996.

The Alexander Project is an ongoing, multicenter surveillance study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens with testing undertaken in a central laboratory. During the period 1992-1995, isolates were collected from geographically separate centers in countries of the EU and various states in the USA. In 1996, the project was extended to centers in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not previously included. Within Europe, France and Spain are established as centers with a high prevalence of both penicillin-intermediate (MIC 0.12-1 mg/l) and resistant (MIC > or = 2 mg/l) strains of Streptococcus pneumoniae, with combined resistance rates in excess of 40% in Toulouse and Barcelona in 1996. Combined rates of intermediate and resistant strains in excess of 10% were found in 1996, the first year of sampling, in Belgium, Switzerland, the Slovak Republic and Hungary. Penicillin resistance has evolved in the USA during the period of study, with rates for combined pneumococcal isolates increasing from 5.6% in 1992 to 16.4% in 1996. Of the new, non-European centers joining the project in 1996, Mexico (intermediate 31.4%, resistant 15.7%) and, in particular, Hong Kong (intermediate 9.1%, resistant 50%) are centers with a high prevalence of penicillin resistance. Macrolide resistance has increased generally among pneumococcal isolates examined during the study period, both in penicillin-susceptible and resistant isolates, and was evident in 16.5% of the 2160 isolates collected during 1996. In four centers (London, UK; Genoa, Italy; Pokfulum, Hong Kong; Leuven, Belgium), macrolide resistance rates exceeded those of combined penicillin-intermediate and resistant strains; in 12/19 centers (63.2%) macrolide resistance was more prevalent than penicillin resistance. In 1996, macrolide resistance was found in excess of 10% of isolates in Poland, Hungary, London, UK, combined USA isolates, the Slovak Republic, Barcelona, Spain, Genoa, Italy, Mexico, Toulouse, France and Pokfulum, Hong Kong. beta-lactamase production was the principal mechanism of resistance found among isolates of Haemophilus influenzae, with rates in 1996 of around 20% or more in France, Belgium and Spain, and in excess of 10% in the UK and the Czech Republic. In the same year in non-European centers, Mexico (25%), Saudi Arabia (27.9%), Hong Kong (37.1%) and the USA (30.4% of combined isolates) had a high prevalence of beta-lactamase production. Isolates of beta-lactamase-negative, ampicillin-resistant H. influenzae were generally very uncommon, with only Barcelona, Spain consistently associated with rates in excess of 1%. beta-lactamase production in Moraxella catarrhalis was observed in over 90% of isolates tested in 1996.

Anti-Bacterial Agents↗
PubMed1998

European Glycopeptide Susceptibility Survey of gram-positive bacteria for 1995. European Glycopeptide Resistance Survey Study Group.

In the European Glycopeptide Susceptibility Survey 7078 Gram-positive isolates collected in 1995 from 70 centers in 9 countries of Western Europe were examined, using a standardized, quantitative susceptibility testing method. Of the 7078 isolates, 6824 (96.4%) were tested by the national coordinating centers. Teicoplanin (mode MIC 0.5 microgram/mL) was generally twice as active as vancomycin (mode MIC 1 microgram/mL) against Staphylococcus aureus (n = 2852). All isolates were susceptible to vancomycin (MIC < or = 4 micrograms/mL) and all but four to teicoplanin (MIC < or = 8 micrograms/mL); these four isolates were of intermediate susceptibility (MIC 16 micrograms/mL). With coagulase-negative staphylococci (n = 1444), the distribution of MIC of teicoplanin was wider than for vancomycin. Two and two-tenths percent of coagulase-negative staphylococci excluding Staphylococcus haemolyticus required 16 micrograms/mL teicoplanin for inhibition (intermediate) and 0.4% > or = 32 micrograms/mL (resistant). Among isolates of S. haemolyticus, 4.4% were of intermediate susceptibility (MIC 16 micrograms/mL) and 3.3% were resistant (MIC > or = 32 micrograms/mL) to teicoplanin. However, this species represented only 6.3% of the isolates of coagulase-negative Staphylococcus spp. Generally, teicoplanin (mode MIC < or = 0.12 microgram/mL) was four to eight times more active than vancomycin (mode MIC < or = 0.5 microgram/mL) against the 770 streptococcal isolates. Glycopeptide-susceptible Enterococcus spp. (n = 1695) were generally four times more susceptible to teicoplanin (mode MIC 0.25 microgram/mL) than to vancomycin (mode MIC 1 microgram/mL). Combined vancomycin and teicoplanin (VanA phenotype) resistance was observed more frequently (9.3%) in isolates of Enterococcus faecium than in Enterococcus faecalis (0.8%). Four isolates of unspeciated enterococci (1.4%) also expressed this resistance phenotype. Four isolates of E. faecium and four of E. faecalis expressed the VanB-type (low-level, vancomycin only) resistance. Spain was the only country not to submit resistant E. faecium strains while resistant E. faecalis isolates came only from Spain and Italy.

Anti-Bacterial Agents↗
PubMed1998

The Nearchus project: antibiotic susceptibility of respiratory pathogens and clinical outcome in lower respiratory tract infections at 27 centres in the UK.

Community-acquired respiratory infections are usually treated empirically by the primary care physician. Increasing antibiotic resistance, for example, in pneumococci, prompted a UK survey of antibiotic susceptibility of three major lower respiratory tract pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Each of 27 centres was asked to collect up to 100 isolates of the three species and submit them for confirmation of identity and for susceptibility testing to a central laboratory. In addition, general practitioners were asked for demographic details on the patient, their treatment and the clinical outcome. Of 1689 viable pathogens collected, there were 1078 (64%) strains of H. influenzae, 258 (15%) of M. catarrhalis and 353 (21%) of S. pneumoniae. Production of beta-lactamase was detected in 163 (15%) of 1078 isolates of H. influenzae and in 243 (94%) isolates of M. catarrhalis. For S. pneumoniae, moderate resistance to penicillin (MIC 0.12-1 mg/l) was found in 12 (3.4%) isolates and high level resistance (MIC > or = 2 mg/l) in 13 (3.7%) isolates. The most common individual treatments were amoxycillin, amoxycillin/clavulanate (amoxyclav) , and erythromycin. Complete or partial clinical resolution was achieved in 88% of 809 patients infected with H. influenzae, 83% of 197 infected with M. catarrhalis and 90% of 255 infected with S. pneumoniae.

Anti-Bacterial Agents↗
PubMed1998

Antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens isolated in the UK during the 1995-1996 cold season.

The antimicrobial susceptibility of 1078 isolates of Haemophilus influenzae, 348 Streptococcus pneumoniae and 258 Moraxella catarrhalis was determined. Overall 15.1% of H. influenzae produced beta-lactamase; 98.8% were susceptible to co-amoxiclav, 85.8% to cefaclor, 96% to clarithromycin and 100% to ciprofloxacin. The majority (94.2%) of M. catarrhalis produced beta-lactamase. The overall prevalence of low-level penicillin resistance (MIC = 0.12-1 mg/L) amongst isolates of S. pneumoniae was 3.4% and that of high-level resistance (MIC > or = 2 mg/L) was 3.7%. Most (96.3%) of the isolates of S. pneumoniae were susceptible to amoxycillin (MIC < or = 0.5 mg/L), 96% to cefaclor (MIC < or = 8 mg/L), 90.7% to clarithromycin (MIC < or = 0.25 mg/L) and 89% to ciprofloxacin (MIC < or = 1 mg/L).

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1997

In-vitro activity of trovafloxacin, a new fluoroquinolone, against recent clinical isolates.

Trovafloxacin (CP-99,219) was very active against Gram-negative species examined including Haemophilus influenzae, Moraxella catarrhalis, Legionella spp., Neisseria spp. and Escherichia coli (MIC90s < or = 0.03 mg/L). In general trovafloxacin was twice as active as ofloxacin but only half as active as ciprofloxacin against Gram-negative species. Trovafloxacin was active against Gram-positive organisms, including Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Enterococcus faecalis (MIC90s < or = 0.25 mg/L). Against these organisms activity was eight to 16 times greater for trovafloxacin than for either ofloxacin or ciprofloxacin. In addition, Chlamydia spp., Mycoplasma spp. and Ureaplasma urealyticum were eight to 16 times more susceptible to trovafloxacin than to either ofloxacin or ciprofloxacin. These in-vitro data show that trovafloxacin is a broad-spectrum fluoroquinolone with greater activity against clinically important Gram-positive species compared with ofloxacin or ciprofloxacin.

Anti-Infective Agents↗
PubMed1997

The in-vitro activity of grepafloxacin against Chlamydia spp., Mycoplasma spp., Ureaplasma urealyticum and Legionella spp.

The activity of grepafloxacin, a new orally active fluoroquinolone, was compared with the activities of ofloxacin, clarithromycin and doxycycline against Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Mycoplasma hominis and Ureaplasma urealyticum, and with the activities of ofloxacin, clarithromycin and rifampicin against Legionella spp. Grepafloxacin (MIC range 0.06-0.12 mg/L) was some 8-16 times more active than ofloxacin against the chlamydiae, showing activity similar to that of doxycycline, and equal or two- to four-fold less active than clarithromycin. Grepafloxacin was four-fold more active than ofloxacin against M. pneumoniae (MIC 0.06-0.5 mg/L) and U. urealyticum (MIC 0.12-1.0 mg/L), but 16 times more active against M. hominis (MIC 0.015-0.05 mg/L). Grepafloxacin was highly active against Legionella spp. (MIC 0.008-0.03 mg/L), showing equivalent activity to ofloxacin, clarithromycin and rifampicin.

Anti-Bacterial Agents↗
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↗