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Biomedical subjects

K E Bowker

Publications and source records attributed to K E Bowker.

At least 19 recordsLinked to original sources
PubMed2002

Direct measurement of bacterial penetration through surgical gowns: a new method.

There is a paucity of data on the penetration of bacteria through surgical gowns during operations. A simple new method was developed, using Petri dishes filled with horse blood agar that were attached to the outside of the gown material. This was used to assess bacterial penetration through disposable spun-bonded polyester gowns and re-usable woven polyester gowns during normal use. There was a significant difference between the two gown types when tested in the axilla (P = 0.02), the groin (P = 0.02) and the peri-anal region (P < 0.01), with the disposable gowns performing to a higher standard. Re-usable gowns demonstrated variation in penetrability, and for this reason, may be unsuitable for use in orthopaedic implant surgery.

Bacteria↗
PubMed2002

Effect of jewellery on surface bacterial counts of operating theatres.

Twenty items of three jewellery types were studied. Finger rings, nose and ear piercings increased local surface bacterial counts when in situ, and especially after removal (P<0.0001). Although in the UK the National Association of Theatre Nurses' guidelines suggest that all jewellery should be removed before scrubbing, we suggest that jewellery worn on noses and ears should be left in situ and covered by masks and hats, respectively. The effect of jewellery on skin disinfection needs further study before guidelines can be made concerning finger rings.

Bacteria↗
PubMed2002

BAL 9141, a new broad-spectrum pyrrolidinone cephalosporin: activity against clinically significant anaerobes in comparison with 10 other antimicrobials.

The in vitro potency of BAL 9141, a new pyrrolidinone cephalosporin, was tested against non-duplicate strains of anaerobic bacteria. The MIC(50) was 1 mg/L against Actinomyces species, Clostridium species, Gram-positive anaerobic cocci, Porphyromonas species, Fusobacterium species, Lactobacillus species, Prevotella species and Veillonella species. The MIC(50) was 16 mg/L for Bacteroides fragilis and other Bacteroides species. BAL 9141 was not active against cefoxitin-resistant Bacteroides fragilis.

Bacteria, Anaerobic↗
PubMed2001

The activity of vancomycin against heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus explored using an in vitro pharmacokinetic model.

Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) may account for treatment failure with vancomycin and act as a precursor of vancomycin-intermediate or -resistant S. aureus. The activity of vancomycin was assessed against vancomycinsusceptible, hVISA and VISA strains in a dilutional pharmacokinetic model. Over a 48 h period, total bacteria and cells with a vancomycin-intermediate phenotype were quantified. Total counts of hVISA were reduced by vancomycin in a similar way to a vancomycin-susceptible control. The vancomycin-intermediate sub-population was eradicated from the model within one dose interval. Exposure to low vancomycin concentrations did not result in an increase in the proportion of cells which were vancomycin intermediate. Short-term exposure of hVISA to vancomycin at gradient concentrations did not increase the proportion of cells with vancomycin-intermediate phenotype.

Anti-Bacterial Agents↗
PubMed2001

Pharmacodynamics of gemifloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model of infection.

The pharmacodynamics of gemifloxacin against Streptococcus pneumoniae were investigated in a dilutional pharmacodynamic model of infection. Dose fractionation was used to simulate concentrations of gemifloxacin in human serum associated with 640 mg every 48 h (one dose), 320 mg every 24 h (two doses), and 160 mg every 12 h (four doses). Five strains of S. pneumoniae for which MICs were 0.016, 0.06, 0.1, 0.16, and 0.24 mg/liter were used to assess the antibacterial effect of gemifloxacin. An inoculum of 10(7) to 10(8) CFU/ml was used, and each experiment was performed at least in triplicate. The pharmacodynamic parameters (area under the concentration-time curve [AUC]/MIC, maximum concentration of drug in serum [C(max)]/MIC, and the time that the serum drug concentration remains higher than the MIC [T > MIC]) were related to antibacterial effect as measured by the area under the bacterial-kill curve from 0 to 48 h (AUBKC(48)) using an inhibitory sigmoid E(max) model. Weighted least-squares regression was used to predict the effect of the pharmacodynamic parameters on AUBKC(48), and Cox proportional-hazards regression was used to predict the effect of the three pharmacodynamic parameters on the time needed to kill 99.9% of the starting inoculum (T99.9). There was a clear relationship between strain susceptibility and clearance from the model. The simulations (160 mg every 12 h) were associated with slower initial clearance than were the other simulations; in contrast, bacterial regrowth occurred with the 640-mg simulation when MICs were > or =0.1 mg/liter. The percentage coefficient of variance was 19% for AUBKC(48), and the inhibitory sigmoid E(max) model best fit the relationship between AUBKC(48) and AUC/MIC. C(max)/MIC and T > MIC fit less well. The maximum response occurred at an AUC/MIC of >300 to 400. In weighted least-squares regression analysis, there was no evidence that C(max)/MIC was predictive of AUBKC(48), but both AUC/MIC and T > MIC were. A repeat analysis using only data for which the T > MIC was >75% and for which hence regrowth was minimized indicated that AUC/MIC alone was predictive of AUBKC(48). Initial univariate analysis indicated that all three pharmacodynamic parameters were predictive of T99.9, but in the multivariate model only C(max)/MIC reached significance. These data indicate that gemifloxacin is an effective antipneumococcal agent and that AUC/MIC is the best predictor of antibacterial effect as measured by AUBKC(48). However, C(max)/MIC is the best predictor of speed of kill, as measured by T99.9. T > MIC also has a role in determining AUBKC(48), especially when the dose spacing is considerable. Once-daily dosing seems most suitable for gemifloxacin.

Anti-Infective Agents↗
PubMed2000

Use of meropenem 3 g once daily for outpatient treatment of infective exacerbations of bronchiectasis.

Meropenem administered as a single iv 3 g dose once every 24 h was used to treat nine ambulatory patients with infective exacerbations of bronchiectasis. Serum meropenem concentrations were measured before dosing and at 30 min after each 30 min infusion. Mean pre-dose concentrations were <0.1 mg/L and mean post-dose concentrations 93.9 +/- 29.5 mg/L (95% confidence interval (CI) 86. 2-101.6, n = 59). A pathogen was cultured from sputum in six patients and eradicated (<100 cfu/g sputum) in all but one by day 6 of therapy. Previous work on animals has shown that a bacteriostatic effect is seen with meropenem when t > MIC is greater than 20-30% of the dose interval. In these nine patients, this could be achieved and was associated with successful outcome for pathogens for which MICs are </= 0.5 mg/L. Therefore, once-a-day meropenem therapy may be a useful option for outpatient treatment for isolates for which MICs are </= 0.5 mg/L.

Aged↗
PubMed1999

Use of a clinical Escherichia coli isolate expressing lux genes to study the antimicrobial pharmacodynamics of moxifloxacin.

Escherichia coli isolate 16,906 expressing lux genes was used for real-time monitoring of moxifloxacin effects on bacterial metabolism compared with effects on cell replication. Viable counts showed concentration-dependent killing by moxifloxacin; real-time measurement of bioluminescence on the same cultures showed metabolic activity over 54 h, but with greater inhibition at 1 x MIC than with higher MIC multiples. Post-antibiotic effect was longer when determined using bioluminescence than by viable counts. The control-related effective regrowth time was consistent with both methods. Bioluminescent bacteria provide a rapid and sensitive means for measuring antimicrobial effects on bacterial metabolism.

Anti-Bacterial Agents↗
PubMed1999

In-vitro activity of HMR 3647 against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and beta-haemolytic streptococci.

The in-vitro activity of HMR 3647 and seven comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, penicillin G, ciprofloxacin and levofloxacin) were tested against 207 Streptococcus pneumoniae and 200 beta-haemolytic streptococci. Ten comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, ampicillin, co-amoxiclav, cefuroxime, cefotaxime, ciprofloxacin and levofloxacin) were tested against 143 Haemophilus influenzae and 58 Moraxella catarrhalis. The MIC50 of HMR 3647 for S. pneumoniae was < or =0.008 mg/L, less than that for the macrolides or quinolones tested. Pneumococci with an erythromycin A MIC of 0.06 mg/L (n = 23) had an MIC50 of HMR 3647 < or =0.008 mg/L, whereas isolates with an erythromycin A MIC > or =1 mg/L (n = 34) had an MIC50 of HMR 3647 of 0.03 mg/L, a four-fold increase. In contrast, the difference in macrolide MIC50s for the two groups was > or =64-fold. The MIC50s foro beta-haemolytic streptococci, classified by Lancefield group, were in the range 0.015 to 0.06 mg/L for HMR 3647. H. influenzae were categorized into three groups according to cefuroxime MIC: <1 mg/L (n = 72); 2-4 mg/L (n = 29); and >4 mg/L (n = 42). The MIC50 of HMR 3647 increased two-fold with increasing cefuroxime MICs; beta-lactam MICs increased much more markedly. The MIC50 of HMR 3647 for M. catarrhalis was 0.03 mg/L. HMR 3647 has good activity against respiratory tract pathogens but in-vitro susceptibility is affected by erythromycin A susceptibility in S. pneumoniae and beta-haemolytic streptococci.

Anti-Bacterial Agents↗
PubMed1999

Comparison of in-vitro pharmacodynamics of once and twice daily ciprofloxacin.

The pharmacodynamics of ciprofloxacin were explored in an in-vitro continuous bacterial culture model of infection, by simulating two oral dosing regimens; 0.5 g 12-hourly (bd) and 1 g 24-hourly (od). Three strains of Escherichia coli (ciprofloxacin MICs 0.03, 0.5 and 2 mg/L); two strains of Pseudomonas aeruginosa (MICs 0.09 and 1.5 mg/L), two strains of Staphylococcus aureus (MICs 0.12 and 1 mg/L) and two strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L) were used. Three pharmacodynamic parameters, T > MIC, C(max)/MIC and AUC/MIC (T = time, C(max) = peak serum concentration, AUC = area under the curve), were compared with area under the bacterial-kill curve (AUBKC) (after transformation of the AUBKC) using a simple E(max) or sigmoidal E(max) model. AUBKC was taken to be the main antibacterial effect measure. The models were compared by inspection of residuals and Akaike information criterion. E(max) models adequately described the relationship between AUC/MIC and AUBKC and between C(max)/MIC and AUBKC, but not between T> MIC and AUBKC. All three pharmacodynamic parameters are related to each other but multiple regression analysis indicated that AUC/MIC was the best individual predictor of AUBKC. Despite this, comparison of od and bd regimens indicates some advantage to od in terms of early antibacterial effect. Serum concentration-time curve shape has some importance in determining antibacterial effect. These data indicate that for ciprofloxacin AUC/MIC ratio is not the sole determinant of antibacterial effect.

Anti-Infective Agents↗
PubMed1999

Exploration of the in-vitro pharmacodynamic activity of moxifloxacin for Staphylococcus aureus and Streptococci of lancefield groups A and G.

The serum concentrations associated with the oral administration of 400 mg moxifloxacin every 24 h over 48 h in man were simulated in an in-vitro dilutional, continuous bacterial culture model of infection. The initial inoculum was 5 x 10(7)-5 x 10(8) cfu/mL and all strains were tested on at least three occasions. Two strains of Staphylococcus aureus (one methicillin susceptible, the other resistant) with moxifloxacin MICs 0.14 mg/L and 0.06 mg/L and two strains of beta-haemolytic streptococci, Lancefield Group A, MIC 0. 16 mg/L and Group G, MIC 0.4 mg/L were used. In addition, two laboratory-generated mutants with raised moxifloxacin MICs were also employed: methicillin-sensitive S. aureus (MSSA) MIC 1.0 mg/L and Group A streptococcus MIC 1.8 mg/L. The antibacterial effect of moxifloxacin was judged by changes in viable count over time, and the area under the bacterial-kill curve (AUBKC) after 24 and 48 h. For S. aureus MIC 0.14 mg/L the AUBKC(24) (log cfu/mL.h) was 77.8 +/- 4.6 and AUBKC(48) 92.0 +/- 6.9. For its mutant, moxifloxacin MIC 1.0 mg/L, the AUBKC(24) was 116.1 +/- 15.6 and AUBKC(48) 211.9 +/- 23.1, indicating decreased killing. AUBKC(24) and AUBKC(48) values of 110.7 +/- 10.3 and 130.9 +/- 21.3, respectively, were noted for the MRSA strain. The Group A streptococcus, MIC 0.16 mg/L, had an AUBKC(24) of 91.4 +/- 19.4 and AUBKC(48) of 157.0 +/- 70.9. The mutant, MIC 1.8 mg/L, had an AUBKC(24) of 127.0 +/- 1.9 and AUBKC(48) of 205.1 +/- 6.4. Despite a lower MIC (0.4 mg/L) the single strain of Group G streptococcus tested was killed poorly, AUBKC(24) 139.9 +/- 3.6 and AUBKC(48) 252.3 +/- 18.6. The pharmacodynamic parameters AUC/MIC, T > MIC, (AUC > MIC)/MIC (AUC = area under the curve, T = time) and WAUC ((AUC/MIC) (T > MIC/100)) (WAUC = weighted area under the curve) were related to AUBKC(24) and AUBKC(48) using an inhibitory sigmoid E(max) model. T > MIC was poorly related to AUBKC (r = 0.36) while AUC/MIC, (AUC > MIC)/MIC and WAUC were strongly related to AUBKC(24) (r = 0.75-0.79) and AUBKC(48) (r = 0.78-0.84). The maximum antibacterial effect was achieved with an AUC/MIC ratio of 150-200. AUC-related pharmacodynamic parameters predicted antibacterial effect better than T > MIC.

Anti-Infective Agents↗
PubMed1999

Activity of moxifloxacin, administered once a day, against Streptococcus pneumoniae in an in vitro pharmacodynamic model of infection.

The antibacterial effect of moxifloxacin was studied by using an in vitro pharmacodynamic model of infection with dosing simulations of 400 mg every 24 h for 48 h. Streptococcus pneumoniae was tested by using four wild-type strains for which the moxifloxacin MICs were 0. 008, 0.12, 0.14, and 3.6 mg/liter. In addition, two isogenic mutants, generated from the strains for which the moxifloxacin MICs were </=0.12 mg/liter and for which the MICs were 1.0 and 1.6 mg/liter, were also used. Antibacterial efficacy was measured by the following indices: log change in viable count at 12, 24, 36, and 48 h; area under the bacterial kill curve (AUBKC); and time to kill 99.9% of the initial inoculum. With the three strains for which the moxifloxacin MICs were </=0.14 mg/liter, there was a marked reduction in viable count over 12 to 36 h; in contrast, with strains for which the MICs were >/=1.0 mg/liter, little killing occurred over 48 h. A sigmoid dose-response model indicated that the area under the curve/MIC ratio was strongly related to the log change in viable count at 24 and 48 h and to the AUBKC. These data indicate that moxifloxacin may have a role in management of S. pneumoniae infection.

Anti-Infective Agents↗
PubMed1998

Sequential antimicrobial therapy: pharmacokinetic and pharmacodynamic considerations in sequential therapy.

The pharmacodynamic factors important in sequential therapy are largely unknown. This is because most pharmacodynamic investigations concentrate on how bacterial populations respond to first antimicrobial exposures. However, it is likely that for B lactams T>MIC and for quinolones the antimicrobial AUC/MIC ratio will be important. Factors which reduce antimicrobial absorption will impact on these parameters and require further study.

4-Quinolones↗