Biomedical subjects

R N Jones

Publications and source records attributed to R N Jones.

At least 55 records · Page 3Linked to original sources

PubMed2003

Antimicrobial activity against strains of Escherichia coli and Klebsiella spp. with resistance phenotypes consistent with an extended-spectrum beta-lactamase in Europe.

Extended-spectrum beta-lactamases (ESBLs) have continued to evolve after their initial detection in Europe nearly two decades ago. The summary results from the MYSTIC Program (31 medical centers) were utilized to assess the extent of ESBL occurrence in Europe from 1997 to 2000. ESBL phenotype rates in Klebsiella spp. (32.8%) and Escherichia coli (14.4%) were generally stable, but extensive hospital-to-hospital and unit-to-unit variations were noted. The highest ESBL rates were found in eastern Europe (including Turkey) and in intensive care unit patient populations. Carbapenems remained active against the ESBL-producing strains (meropenem MIC90, 0.25-1 mg/L), while some other agents, such as aminoglycosides, fluoroquinolones, and piperacillin-tazobactam, were significantly less effective. International surveillance initiatives should be maintained to monitor future progression of this important resistance.

Anti-Bacterial Agents↗

PubMed2003

Validation of commercial dry-form broth microdilution panels for susceptibility testing of AZD2563, a new long-acting oxazolidinone.

The MIC results using a dry-form broth microdilution panel (TREK Diagnostic/Sensititre, Westlake, OH, USA) were validated for AZD2563, a novel oxazolidinone compound. In comparision studies against reference frozen-form panels, the commercial MIC results were the same as the reference calue for 82.7% of organisms and all results were within +/- one log2 dilution. Using 462 organisms, most from three genus groups (enterococci, staphylococci, streptococci), test results indicate that Sensititre MIC values were comparable to the reference test and can be utilized in clinical trials of for routine laboratory use when testing AZD2563 and linezolid, the drug class comparator.

Anti-Bacterial Agents↗

PubMed2003

Antimicrobial activity of LB10827, a new orally administered cephalosporin, tested against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.

A new orally administered cephalosporin, LB10827, was compared to 16 other antimicrobial agents tested against Streptococcus pneumoniae (520 strains), Haemophilus influenzae (302 strains) and Moraxella catarrhalis (188 strains) by reference broth microdilution methods. LB10827 (MIC90, 0.12 mg/L; highest MIC, 0.5 mg/L) was 8-16-fold more potent than cefdinir, cefpodoxime or cefuroxime when tested against S. pneumoniae. All Gram-negative strains were inhibited at </= 0.5 mg/L LB10827, which is an activity equal or superior to that of currently available and tested oral beta-lactams. LB10827 appears to be a promising agent worthy of continued investigations both in vitro and in vivo.

Administration, Oral↗

PubMed2003

Revision of linezolid disk diffusion quality control guidelines for testing Staphylococcus aureus ATCC 25923: an independent seven-laboratory trial.

The accuracy of the published disk diffusion quality control (QC) range for linezolid for Staphylococcus aureus ATCC 25923 has been reported to be problematic, prompting a multicenter study to determine if revision was necessary. Five out of seven laboratories reported values outside the current QC range. Three participants had significant (13.3-60.0%) 'unacceptable' results with zones smaller than the established range. Overall, a range of 21-32 mm was shown (82.4% within the NCCLS published range). A revision (25-31 mm; 95.7% of results) of the QC range is necessary when testing S. aureus ATCC 25923 against linezolid.

Acetamides↗

PubMed2003

Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci.

BAL9141 has been reported to have inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), many enterococci, and streptococci with various resistant patterns. BAL9141 potency was assessed by time-kill curves alone or with subinhibitory concentrations of gentamicin (MIC/4). BAL9141 exhibited bactericidal activity alone against all the streptococci and staphylococci. Among ampicillin-susceptible enterococci, BAL9141 was bactericidal against some strains, but no BAL9141 inhibition was observed of ampicillin-resistant Enterococcus faecium. The activity of BAL9141 with gentamicin was slightly enhanced (not synergy) or indifferent against staphylococci. BAL9141 demonstrated bactericidal action alone against Enterococcus faecalis and some E. faecium strains (-4.8 to -6.0 log10 CFU/mL), but static effects were also noted. Drug interactions with gentamicin showed early synergy (4-8 h) for all enterococci, and indifference or synergy at 24 h (no antagonism). BAL9141 (< or = 8 mg/L) showed promising bactericidal activity alone and synergy with gentamicin against some of the vancomycin-resistant enterococci tested.

Anti-Bacterial Agents↗

PubMed2003

Relationship of asthma to irritant gas exposures in pulp and paper mills.

The potential of chronic or acute irritant gas exposures to cause asthma or a variant condition, reactive airways dysfunction syndrome (RADS) was investigated by observing asthma incidence in a large working population, using person-years at risk (P-YR) to compute relative rates (RR). Health data came from employee examinations at 62 pulp and paper plants. The 39122 workers who denied asthma beginning before the observation period included: 19326 denying irritant exposures, with no gassing exposures; 19349 with self-reported irritant exposures, and no gassing; and 447 with documented gassings. Asthma was defined as self-reported asthma beginning after the start of observation. P-YR accrued from September 29, 1986, for the nonexposed and exposed workers, and from date of first gassing for gassed workers, and ended with disease onset in any who developed asthma. RR of asthma with 95% confidence intervals (CI95) were calculated for the exposed and gassed groups, relative to the nonexposed. Exposed (nongassed) workers had an elevated asthma rate, RR=1.48, CI95=1.17-1.86, after adjustment for effects of gender and number of examinations. The rate in gassed workers was not significantly elevated: RR=1.95, CI95=0.75-5.08. Of the five asthma cases occurring after gassings, none conformed to diagnostic criteria for RADS. Chronic exposures were associated with increased rate of asthma onset, which must be interpreted with caution because self-reported data defined both exposure category and disease. Documented gassings were not associated with significantly increased rate, and none of 447 gassed persons developed RADS.

Adult↗

PubMed2003

Racial bias in the assessment of cognitive functioning of older adults.

This study was undertaken to determine if the difference in assessed cognition between Black/African-American and White older adults was due differential item functioning (DIF) and/or differences in the effect of background variables. Participants were 15257 adults aged 50 and older surveyed in the Study of Asset and Health Dynamics of the Oldest Old (AHEAD) and Health and Retirement Study (HRS). The cognitive measure was a modified telephone interview for cognitive status. The analytic strategy was a multiple group structural equation model grounded in item response theory. Results suggest that most (89%) of the group difference could be attributed to measurement or structural differences, the remainder being not significantly different from zero (p=0.193). Most items displayed racial DIF, accounting for most of the group difference. After controlling for DIF, the group difference that remained could be attributed to heterogeneity in the effect of background variables. For example, low education was more deleterious for Black/African-Americans, and high income conferred an advantage only for Whites. These findings underscore the importance of efforts to generate culture-fair measurement devices. However, culture-fair assessments may attenuate, but not eliminate, group differences in assessed cognition due to the incommensurate action of background variables

Black or African American↗

PubMed2003

Prevalence of extended-spectrum beta-lactamase-producing Enterobacter cloacae in the Asia-Pacific region: results from the SENTRY Antimicrobial Surveillance Program, 1998 to 2001.

Enterobacter cloacae strains from hospitalized patients with a range of infections were collected by 17 laboratories in the Asia-Pacific region and South Africa. Isolates for which ceftriaxone MICs were above 1 microg/ml and/or ceftazidime MICs were above 2 microg/ml, as well as 46 strains for which ceftriaxone and/or ceftazidime MICs were at or below these values, were screened for levels of extended-spectrum beta-lactamase (ESBL) production through the use of broth microdilution for the detection of clavulanate enhancement of the activity of ceftriaxone, ceftazidime, and cefepime. Of the isolates examined, ceftriaxone and/or ceftazidime had elevated MICs for 44%, of which 36% were ESBL positive. ESBL-positive strains were commonly susceptible to piperacillin-tazobactam and more frequently resistant to several other antimicrobials studied. A cefepime MIC above 0.25 microg/ml had the highest sensitivity (100%) and specificity (74%) for predicting the presence of an ESBL.

Asia↗

PubMed2003

In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazole-resistant isolates.

Caspofungin is an echinocandin antifungal agent with broad-spectrum activity against Candida and Aspergillus spp. The in vitro activities of caspofungin against 3,959 isolates of Candida spp. obtained from over 95 different medical centers worldwide were compared with those of fluconazole and itraconazole. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the NCCLS method using RPMI 1640 as the test medium. Caspofungin was very active against Candida spp. (MIC at which 90% of the isolates were inhibited [MIC(90)], 1 micro g/ml; 96% of MICs were < or =2 micro g/ml). Candida albicans, C. dubliniensis, C. tropicalis, and C. glabrata were the most susceptible species of Candida (MIC(90), 0.25 to 0.5 micro g/ml), and C. guilliermondii was the least susceptible (MIC(90), >8 micro g/ml). Caspofungin was very active against Candida spp., exhibiting high-level resistance to fluconazole and itraconazole (99% of MICs were < or =1 micro g/ml). These results provide further evidence for the spectrum and potency of caspofungin activity against a large and geographically diverse collection of clinically important isolates of Candida spp.

Anti-Bacterial Agents↗

PubMed2003

Pharmacokinetics-pharmacodynamics of cefepime and piperacillin-tazobactam against Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases: report from the ARREST program.

The frequency of resistance to beta-lactams among nosocomial isolates has been increasing due to extended-spectrum beta-lactamase (ESBL)-producing enteric bacilli. Although clinical outcome data are desirable, assessment of clinical efficacy has been limited due to the lack of a statistically meaningful number of well-documented cases. Since time above the MIC (T>MIC) is the pharmacokinetic-pharmacodynamic (PK-PD) measure that best correlates with in vivo activity of beta-lactams, a stochastic model was used to predict the probability of PK-PD target attainment ranging from 30 (P30) to 70% (P70) T>MIC, for standard dosing regimens of both piperacillin-tazobactam and cefepime against Escherichia coli and Klebsiella pneumoniae ESBL phenotypes. The P70/30 T>MIC for cefepime at 2 g every 12 h against E. coli and K. pneumoniae was 0.99/1.0 and 0.96/1.0 and for a regimen of 1 g every 12 h was 0.96/1.0 and 0.93/0.99, respectively. For piperacillin-tazobactam at 3.375 g every 4 h against E. coli and K. pneumoniae, the P70/30 T>MIC was 0.77/0.96 and 0.48/0.77 and for a regimen of 3.375 g every 6 h was 0.28/0.91 and 0.16/0.69, respectively. These data suggest that the probability of achieving T>MIC target attainment rates is generally higher with cefepime than with piperacillin-tazobactam for present-day ESBL-producing strains when one uses contemporary dosing regimens.

Cefepime↗

PubMed2003

Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans.

Strains of Cryptococcus neoformans expressing heteroresistance to fluconazole have been described previously. The present study was conducted to investigate the prevalence of heteroresistance among clinical isolates of C. neoformans and to characterize the heteroresistant phenotypes. A total of 107 clinical isolates of C. neoformans for which the MICs of fluconazole ranged from 0.25 to 32 microg/ml were selected. The isolates were chosen to represent a broad geographic distribution. Of the 107 C. neoformans isolates tested, 4 grew on medium containing fluconazole at concentrations that were four to eight times higher than the MICs for each strain. A fifth isolate, for which the fluconazole MIC was 32 microg/ml, grew on agar with 64 microg of fluconazole per ml. These five isolates (4.7% of the total number) were confirmed to exhibit heteroresistant compositions by population analysis. The degree and frequency of resistance varied among the isolates. Stepwise selection by exposure to fluconazole resulted in subclones of all five strains for which the fluconazole MIC was >64 microg/ml. Subclones of three strains demonstrated a homogeneous population of resistant cells on medium containing 64 microg of fluconazole/ml. The resistance was sensitive to incubation temperature, that is, heteroresistance was demonstrable only at 30 degrees C by agar-based tests, and was reversible through serial transfers on fluconazole-free medium over a period of 8 days. These results suggest that the fluconazole-heteroresistant phenotype of C. neoformans exists in a significant proportion of clinical isolates and that fluconazole resistance can be developed by selection from heteroresistant clones and induction by exposure to fluconazole.

Antifungal Agents↗

PubMed2003

In vitro activities of voriconazole, posaconazole, and four licensed systemic antifungal agents against Candida species infrequently isolated from blood.

We determined the in vitro susceptibilities of 314 strains of Candida spp., representing 13 species rarely isolated from blood, to posaconazole and voriconazole as well as four licensed systemic antifungal agents (amphotericin B, flucytosine, fluconazole, and itraconazole). The organisms included 153 isolates of C. krusei, 67 isolates of C. lusitaniae, 48 isolates of C. guilliermondii, 10 isolates of C. famata, 10 isolates of C. kefyr, 6 isolates of C. pelliculosa, 5 isolates of C. rugosa, 4 isolates of C. lipolytica, 3 isolates of C. dubliniensis, 3 isolates of C. inconspicua, 2 isolates of C. sake, and 1 isolate each of C. lambica, C. norvegensis, and C. zeylanoides. MIC determinations were made by the National Committee for Clinical Laboratory Standards reference broth microdilution method and Etest (amphotericin B). Resistance to both amphotericin B and fluconazole was observed in strains of C. krusei, C. lusitaniae, C. guilliermondii, C. inconspicua, and C. sake. Resistance to amphotericin B, but not to fluconazole, was also observed among isolates of C. kefyr and C. rugosa. Posaconazole and voriconazole were active (MIC, < or = 1 micro g/ml) against 94 to 100% of these isolates. In contrast to the more common species of Candida causing bloodstream infection, these rare species appear to be less susceptible to the currently licensed systemic antifungal agents, with the exception of voriconazole. Continued surveillance will be necessary to detect the emergence of these species as more prevalent, resistant pathogens. The new triazoles appear to offer acceptable coverage of uncommon Candida sp. bloodstream infections.

Antifungal Agents↗

PubMed2003

Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi.

We examined the in vitro activity of caspofungin, posaconazole, voriconazole, ravuconazole, itraconazole, and amphotericin B against 448 recent clinical mold isolates. The endpoint for reading caspofungin was the minimum effective concentration (MEC). Among the triazoles, posaconazole was most active, inhibiting 95% of isolates at 95% of Aspergillus spp. at <or=1 microg/ml compared to 83% for itraconazole and 91% for amphotericin B. Amphotericin B inhibited only 38% of Aspergillus terreus isolates at <or=1 microg/ml, whereas the three new triazoles and caspofungin inhibited all A. terreus at <or=0.5 microg/ml. The new triazoles and caspofungin have excellent in vitro activity against a very large collection of recent clinical isolates of Aspergillus spp., and some in vitro activity against selected other filamentous fungi.

Amphotericin B↗

PubMed2002

Emerging elevated mupirocin resistance rates among staphylococcal isolates in the SENTRY Antimicrobial Surveillance Program (2000): correlations of results from disk diffusion, Etest and reference dilution methods.

Staphylococci cause one-third of all serious invasive infections in the SENTRY Antimicrobial Surveillance Program including bacteremias and lower respiratory tract infections. Staphylococci are also commensals of the skin and nasal passages; therefore, topical agents active against these organisms are valuable in preventing infections or transfer of the organisms between patients and/or health care workers. Mupirocin is a potent topical anti-staphylococcal compound, but its effectiveness has been compromised by emerging resistance. In early 2000, the SENTRY Program detected 302 mupirocin-resistant isolates (131 Staphylococcus aureus, and 171 coagulase-negative staphylococci [CoNS]) from the United States (19/25 medical centers), Canada (4/5), Latin America (3/9) and Europe (7/18). One hundred sixty-eight mupirocin-resistant and 59 susceptible isolates were tested further by reference MIC, Etest (AB BIODISK, Solna, Sweden) and disk diffusion (5-microg) methods. Mupirocin resistance rates for blood stream infections varied by geographic area: for S. aureus from 1.9 to 5.6%, and for CoNS from 12.8 to 39.9%. Using elevated mupirocin MIC results, two resistant populations were noted: low-level resistance at 8-128 microg/mL and high-level resistance at > or = 1024 microg/mL. Acceptable correlation was observed between Etest and disk diffusion results (r = 0.84) without serious intermethod interpretive errors. High-level resistant isolates had heavy growth with no visible zone around the disk; low-level resistant isolates produced hazy zones of inhibition, and susceptible strains had clear zones of inhibition at > or = 17 mm. As mupirocin resistance can be plasmid-mediated, the prudent and appropriate use of this topical agent is important to minimize the ongoing development of resistance. Local surveillance for emerging mupirocin resistance appears warranted particularly in the United States and Canada, pragmatically using a disk diffusion test screening. Where more precise data are needed, the Etest is a very accurate method for distinguishing mupirocin low-level from high-level resistance patterns.

Anti-Bacterial Agents↗

PubMed2002

AZD2563, a new oxazolidinone: bactericidal activity and synergy studies combined with gentamicin or vancomycin against staphylococci and streptococcal strains.

AZD2563, a novel oxazolidinone, was tested against 10 well characterized multiple-resistant strains of staphylococci and viridans group or beta-hemolytic streptococci using kill curve kinetic methods. Generally, AZD2563 demonstrated bacteriostatic action and modest concentration-dependent cidal activity against a minority of strains of both genera. When combined with gentamicin (MIC/4 concentration), rapid bactericidal action was observed against all streptococci tested, but not against the staphylococci. No enhanced activity was noted when AZD2563 was added to subinhibitory concentrations of vancomycin. Linezolid used as a control, showed the same characteristics, confirming that AZD2563 possesses activity comparable to other agents in the oxazolidinone class. AZD2563 remained active (MIC, < or = 1 microg/ml) against all 10 strains tested.

Anti-Bacterial Agents↗

PubMed2002

Antimicrobial resistance trends in community-acquired respiratory tract pathogens in the Western Pacific Region and South Africa: report from the SENTRY antimicrobial surveillance program, (1998-1999) including an in vitro evaluation of BMS284756.

From 1998 to 1999, a large number of community-acquired respiratory tract isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26 antimicrobial agents using the NCCLS-recommended methods. Overall, 40% of S. pneumoniae isolates were resistant to penicillin with 18% of strains having high-level resistance (MIC > or =2 mg/l). Rates of erythromycin and clindamycin resistance were 41 and 23%, respectively. Penicillin-resistant strains showed high rates of resistance to other antimicrobial agents: 96% to trimethoprim-sulphamethoxazole (TMP-SMX), 84% to tetracycline and 81% to erythromycin. A significant proportion of penicillin-susceptible strains was also resistant to erythromycin (21%), tetracycline (29%) and TMP-SMZ (26%). Small numbers of strains were resistant to levofloxacin (0.7%), trovafloxacin (0.4%) and grepafloxacin (1.3%) where as all strains remained uniformly susceptible to quinupristin/dalfopristin and BMS284756 (MIC(90), 0.06 mg/l), a new desfluoroquinolone. beta-lactamases were, produced by 20% H. influenzae isolates and only rare strains showed intrinsic resistance to amoxycillin. Other beta-lactam agents showed good activity with rates of resistance less than 2% and all isolates showed susceptibility to cefixime, ceftibuten, cefepime and cefotaxime. Rates of resistance to tetracycline and chloramphenicol were also relatively low at 3%. The majority (98%) of M. catarrhalis isolates was found to be beta-lactamase-positive and resistant to penicillins, however, resistance to erythromycin and tetracycline was also low at 1.8%. Both H. influenzae and M. catarrhalis isolates were uniformly susceptible to the new desfluoroquinolone and tested fluoroquinolones.

Anti-Infective Agents↗

PubMed2002

Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, 1997-2000.

We report age-related trends in pathogen frequency and antimicrobial susceptibility from 25,745 bloodstream infections (BSI) due to bacterial pathogens reported from medical centres participating in the North American SENTRY Antimicrobial Surveillance Program between January 1997 and September 2000. Staphylococcus aureus, Escherichia coli and coagulase-negative staphylococci (CoNS) were the most common pathogens, together accounting for 55% of all BSI pathogens during this time period. Among nosocomial BSI, CoNS were the most frequently isolated pathogens in infants less than 1 year of age, but S. aureus increased in frequency with increasing age. Among community-onset BSI pathogens, Streptococcus pneumoniae was the most frequently reported pathogen causing BSI in patients aged 1-5, S. aureus among those aged 6-64, and E. coli predominated at the extremes of age (less than 1 year and > or = 65 years of age). Among key organism: antimicrobial agent combinations evaluated, oxacillin resistance in S. aureus increased with increasing age; conversely, oxacillin resistance among CoNS was highest among children 5 years of age or younger. Penicillin resistance among S. pneumoniae BSI was highest in children younger than 5 years, while vancomycin resistance among Enterococcus spp. predominated among nosocomial BSI in patients over 50 years of age. Important age-related differences exist in species distribution and antimicrobial susceptibility of pathogens causing BSI. This information should be helpful for clinicians as they consider empirical antimicrobial therapy for patients with suspected BSI across the age continuum.

Adolescent↗

PubMed2002

Comparative antimicrobial spectrum and activity of the desfluoroquinolone BMS284756 (T-3811) tested against non-fermentative Gram-negative bacilli.

OBJECTIVE: To compare the in vitro activity of BMS284756, a desfluoroquinolone, with four fluoroquinolones against 129 Pseudomonas aeruginosa strains, 97 Stenotrophomonas/Burkholderia group strains and 43 Acinetobacter spp. strains by three in vitro test methods. METHODS: The activity of BMS284756 was determined using the NCCLS reference broth microdilution method and E test (AB Biodisk, Solna, Sweden). These methods were compared for test accuracy, and 5-microg disk zone diameters were compared for interpretative accuracy using the susceptible breakpoint of < or =4 mg/L recommended by the manufacturer. All strains tested were derived from the 1999-2000 SENTRY Antimicrobial Surveillance Program organism collection. RESULTS: Comparative quinolone potency against P. aeruginosa was as follows: ciprofloxacin (MIC50, 0.25 mg/L) > gemifloxacin (MIC50, 0.5 mg/L) > levofloxacin = gatifloxacin (MIC50, 1 mg/L) > BMS284756 (MIC50, 4 mg/L). The MIC50 value for BMS284756 versus Stenotrophomonas/Burkholderia group was 2 mg/L. This potency was similar to that of other quinolones reported previously. The MIC50 results for the Acinetobacter spp. were ciprofloxacin at >2 mg/L, levofloxacin, gatifloxacin and gemifloxacin at 4 mg/L, and BMS284756 at >4 mg/L, all intermediate or resistant concentrations. The E test results compared favorably with the reference dilution test results for P. aeruginosa, Stenotrophomonas/Burkholderia group, and Acinetobacter spp., with an overall essential agreement of 97.0% +/- 2 log2 dilution steps. E test MIC results tended to be slightly lower when testing Stenotrophomonas/Burkholderia group strains. The disk diffusion method correlated well for P. aeruginosa (r = 0.94), Stenotrophomonas/Burkholderia group (r = 0.84) and Acinetobacter spp. (r = 0.99) strains. CONCLUSIONS: BMS284756 was generally less active than other comparison quinolones when tested against non-fermentative Gram-negative bacilli. Its spectrum remains equivalent only if dosing schedules substantiate a proposed susceptible breakpoint of < or =4 mg/L.

Anti-Infective Agents↗