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Biomedical subjects

R N Jones

Publications and source records attributed to R N Jones.

At least 163 records · Page 9Linked to original sources

In vitro activity of newer fluoroquinolones for respiratory tract infections and emerging patterns of antimicrobial resistance: data from the SENTRY antimicrobial surveillance program.

In 1997, an international surveillance program, SENTRY Antimicrobial Surveillance Program, was initiated with the aim of tracking the emergence of antimicrobial resistance worldwide. Results from reference antimicrobial susceptibility testing of bacterial pathogens (from bloodstream, inpatient and outpatient lower respiratory tract, urinary tract, and skin and soft-tissue infections) were included in an extensive database used to define antimicrobial resistance patterns throughout the world. On the basis of 1997-1999 test results from the Americas, fluoroquinolones continue to demonstrate potent in vitro activity against Enterobacteriaceae and important pathogens (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and atypicals) that cause community-acquired respiratory tract infections. At published breakpoint concentrations, gatifloxacin, levofloxacin, sparfloxacin, grepafloxacin, trovafloxacin, and ciprofloxacin inhibited approximately 100% of H. influenzae isolates, including those that demonstrated resistance to beta-lactams and macrolides. Fluoroquinolones were also active against numerous other gram-negative bacilli and demonstrated high activity against S. pneumoniae and beta-hemolytic or viridans group streptococci. New fluoroquinolones maintain activity against penicillin-resistant strains of S. pneumoniae, with a low overall resistance in this species, even among the most recent (1999) clinical isolates. The SENTRY Antimicrobial Surveillance Program will continue to monitor the antibacterial activity of these newer agents throughout the world, to identify emerging resistant strains and to facilitate possible intervention strategies as these newer compounds are used in the clinic setting.

Anti-Infective Agents↗

Genetic relatedness of multidrug-resistant, methicillin (oxacillin)-resistant Staphylococcus aureus bloodstream isolates from SENTRY Antimicrobial Resistance Surveillance Centers worldwide, 1998.

We reviewed Staphylococcus aureus bloodstream infection isolates from SENTRY centers worldwide during 1998 to evaluate the molecular epidemiology of multiply drug-resistant methicillin (oxacillin)-resistant S. aureus (MDR-MRSA). MDR-MRSA was defined as a S. aureus isolate with a MIC for oxacillin at >2 microg/ml and with four or more additional resistances. A total of 325 unique patient isolates of MDR-MRSA from five continents were analyzed using ribotyping and pulsed-field gel electrophoresis (PFGE). The frequency of MDR-MRSA among all S. aureus BSI isolates ranged from only 2.2% in Canada to 35.6% in the Asia-Pacific region. Forty-eight ribotypes (RT) were distinguished, but over 80% of the isolates were contained within the 10 most prevalent RTs. The most common RT, RT 184.5, which included 30% of all MDR-MRSA, was found on four of five continents. PFGE provided superior discrimination and identified numerous clusters of possible clonal dissemination of MDR-MRSA within individual medical centers and between institutions that are in geographic proximity. In four instances, strains with indistinguishable PFGE patterns were found on more than one continent. The predominant PFGE subtype in South America (RT 893.5/Ia) was isolated from patients at centers in Brazil, Argentina, and Portugal, and closely related subtypes were isolated in Chile and Italy. There is great geographic variation in rates of methicillin- and multidrug-resistance among S. aureus bloodstream isolates worldwide. Although many MDR-MRSA strains group geographically, a few closely related epidemic strains have wide regional and even global range.

Anti-Bacterial Agents↗

De novo evolution of satellite DNA on the rye B chromosome.

The most distinctive region of the rye B chromosome is a subtelomeric domain that contains an exceptional concentration of B-chromosome-specific sequences. At metaphase this domain appears to be the physical counterpart of the subtelomeric heterochromatic regions present on standard rye chromosomes, but its conformation at interphase is less condensed. In this report we show that the two sequence families that have been previously found to make up the bulk of the domain have been assembled from fragments of a variety of sequence elements, giving rise to their ostensibly foreign origin. A single mechanism, probably based on synthesis-dependent strand annealing (SDSA), is responsible for their assembly. We provide evidence for sequential evolution of one family on the B chromosome itself. The extent of these rearrangements and the complexity of the higher-order organization of the B-chromosome-specific families indicate that instability is a property of the domain itself, rather than of any single sequence. Indirect evidence suggests that particular fragments may have been selected to confer different properties on the domain and that rearrangements are frequently selected for their effect on DNA structure. The current organization appears to represent a transient stage in the evolution of a conventional heterochromatic region from complex sequences.

Amino Acid Sequence↗

Retrotransposon evolution in diverse plant genomes.

Retrotransposon or retrotransposon-like sequences have been reported to be conserved components of cereal centromeres. Here we show that the published sequences are derived from a single conventional Ty3-gypsy family or a nonautonomous derivative. Both autonomous and nonautonomous elements are likely to have colonized Poaceae centromeres at the time of a common ancestor but have been maintained since by active retrotransposition. The retrotransposon family is also present at a lower copy number in the Arabidopsis genome, where it shows less pronounced localization. The history of the family in the two types of genome provides an interesting contrast between "boom and bust" and persistent evolutionary patterns.

Amino Acid Sequence↗

Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second year of the SENTRY antimicrobial surveillance program (1998).

The potency and spectrum of various antimicrobial agents tested against 434 bacterial isolates causing urinary tract infection (UTI) in hospitalized patients in Latin America were evaluated. The genotypes of the extended-spectrum beta-lactamase-producing and selected multi-resistant isolates were also evaluated by molecular typing techniques. Escherichia coli (60.4%) was the most common aetiological agent causing UTI, followed by Klebsiella spp. (11.2%) and Pseudomonas aeruginosa (8.3%). In contrast, Enterococcus spp. isolates caused only 2.3% of UTIs. Fewer than 50% of E. coli isolates were susceptible to broad-spectrum penicillins. The resistance rates to ciprofloxacin and the new quinolones were also high among these isolates. The molecular characterization of ciprofloxacin-resistant E. coli showed that most of them have a double mutation in the gyrA gene associated with a single mutation in the parC gene. The Klebsiella pneumoniae isolates studied demonstrated high resistance rates to beta-lactam drugs, including broad-spectrum cephalosporins. The carbapenems were the compounds with the highest susceptibility rate among these isolates (100.0% susceptible) followed by cefepime (91.7% susceptible). Meropenem, imipenem and cefepime were also the most active drugs against Enterobacter spp. Among P. aeruginosa isolates, meropenem (MIC(50), 2 mg/L) was the most active compound, followed by imipenem (MIC(50), 4 mg/L), cefepime (MIC(50), 8 mg/L) and ceftazidime (MIC(50), 16 mg/L). The results presented in this report confirm that bacterial resistance continues to be a great problem in Latin American medical institutions.

Anti-Bacterial Agents↗

Anti-gonococcal activity of gemifloxacin against fluoroquinolone-resistant strains and a comparison of agar dilution and Etest methods.

Gemifloxacin is a novel quinolone with excellent activity against Gram-positive and some Gram-negative pathogens. Its activity was tested against 150 Neisseria gonorrhoeae strains, including 50 ciprofloxacin-resistant isolates, using reference agar dilution and Etest methods. Gemifloxacin was found to be highly potent against ciprofloxacin-susceptible strains (MIC(90) 0.008 mg/L), but was 16-fold less potent against ciprofloxacin-resistant gonococci. The order of quinolone potency against these fluoroquinolone-resistant mutants was: gemifloxacin (MIC(90) 0.12 mg/L) > trovafloxacin (0.25 mg/L) > moxifloxacin = grepafloxacin (0.5 mg/L) > ciprofloxacin (1 mg/L). Etest and reference agar dilution MIC results showed excellent correlation (r = 0.96) and >98% of MICs were within +/-1 log(2) dilution step (essential agreement). The excellent potency of gemifloxacin indicates its potential for the treatment of infections with quinolone-resistant N. gonorrhoeae.

Anti-Infective Agents↗

The protective effect of social engagement on mortality in long-term care.

OBJECTIVES: To examine the effect of social engagement (SE) on mortality in long-term care. DESIGN: A retrospective cohort study. SETTING: A 725-bed long-term care facility. PARTICIPANTS: A total of 927 long-term care residents who had SE measurements and did not have a serious communication problem. MEASUREMENTS: Minimum Data Set information including psychosocial items comprising an internally reliable and valid SE scale, and mortality risk factor measurements. Mortality data during the 1,721-day follow-up period was obtained from facility records. RESULTS: Life table analyses indicate that higher levels of SE are associated with longer survival (P = .0001). Unadjusted proportional hazards analyses show that residents who did not engage socially were 2.3 times more likely to die during the follow-up period compared with residents who were the most socially engaged. Multivariate adjusted analyses showed the protective effect of SE on mortality remained even after simultaneously adjusting for mortality risk factors. Residents who did not engage socially were 1.4 times as likely to die during the follow-up period compared with residents who were the most socially engaged. CONCLUSIONS: Increased levels of SE were associated with longer survival independent of mortality risk factors. SE may be a modifiable risk factor for death among long-term care residents. More research is needed to understand psychological factors that may influence residents' desire and ability to engage socially.

Activities of Daily Living↗

In vitro activities of ravuconazole (BMS-207147) against 541 clinical isolates of Cryptococcus neoformans.

The in vitro activities of the new triazole, ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of Cryptococcus neoformans. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (MIC at which 90% of the isolates are inhibited [MIC(90)], 0.25 microg/ml) was more active than either itraconazole (MIC(90), 0.5 microg/ml) or fluconazole (MIC(90), 8 microg/ml). Among the isolates inhibited by > or =16 microg of fluconazole/ml, 90.2% were inhibited by < or =1 microg of ravuconazole/ml. On the basis of our findings and the favorable pharmacokinetic properties of ravuconazole, we suggest that ravuconazole may be useful for the treatment of infectious diseases due to C. neoformans and that further clinical studies to confirm these promising in vitro results are warranted.

Antifungal Agents↗

Bloodstream infections due to Candida species: SENTRY antimicrobial surveillance program in North America and Latin America, 1997-1998.

An international program of surveillance of bloodstream infections (BSI) in the United States, Canada, and Latin America detected 306 episodes of candidemia in 34 medical centers (22 in the United States, 6 in Canada, and 6 in Latin America) in 1997 and 328 episodes in 34 medical centers (22 in the United States, 5 in Canada, and 7 in Latin America) in 1998. Of the 634 BSI, 54.3% were due to Candida albicans, 16.4% were due to C. glabrata, 14.9% were due to C. parapsilosis, 8.2% were due to C. tropicalis, 1.6% were due to C. krusei, and 4.6% were due to other Candida spp. The percentage of BSI due to C. albicans decreased very slightly in the United States between 1997 and 1998 (56.2 to 54.4%; P = 0.68) and increased in both Canada (52.6 to 70.1%; P = 0.05) and Latin America (40.5 to 44. 6%; P = 0.67). C. glabrata was the second most common species observed overall, and the percentage of BSI due to C. glabrata increased in all three geographic areas between 1997 and 1998. C. parapsilosis was the third most prevalent BSI isolate in both Canada and Latin America, accounting for 7.0 and 18.5% of BSI, respectively. Resistance to fluconazole (MIC, >/=64 microgram/ml) and itraconazole (MIC, >/=1.0 microgram/ml) was observed infrequently in both 1997 (2.3 and 8.5%, respectively) and 1998 (1.5 and 7.6%, respectively). Among the different species of Candida, resistance to fluconazole and itraconazole was observed in C. glabrata and C. krusei, whereas isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to both fluconazole (98.9 to 100% susceptible) and itraconazole (96.4 to 100% susceptible). Isolates from Canada and Latin America were generally more susceptible to both triazoles than U.S. isolates were. Continued surveillance appears necessary to detect these important changes.

Antifungal Agents↗

Development and application of a PCR-based method including an internal control for diagnosis of congenital cytomegalovirus infection.

Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world. We have designed and evaluated an assay that includes an internal control for amplification and detection of CMV DNA in amniotic fluid and neonatal urine samples. We present data on the use of this assay in the diagnosis of congenital CMV infection. A total of 145 amniotic and fetal fluid samples were examined by this assay; 83 were from healthy pregnant women and 62 were from women who were being investigated because of concerns over the pregnancy (diagnostic group). CMV DNA was detected in three amniotic fluid samples from the diagnostic group but was not detected in any samples taken from healthy pregnant women. Thirty-nine urine samples were obtained from 19 neonates with suspected congenital infection; CMV DNA was detected in urine from 6 of these patients. The assay provides useful information about CMV infection in the fetus and the neonate; when used in conjunction with other diagnostic tools it will enable mothers and obstetricians to make informed decisions about the management of pregnancies complicated by CMV infection.

Amniotic Fluid↗

Quality control guidelines for disk diffusion and broth microdilution antimicrobial susceptibility tests with seven drugs for veterinary applications.

This multicenter study proposes antimicrobial susceptibility (MIC and disk diffusion methods) quality control (QC) parameters for seven compounds utilized in veterinary health. Alexomycin, apramycin, tiamulin, tilmicosin, and tylosin were tested by broth microdilution against various National Committee for Clinical Laboratory Standards (NCCLS)-recommended QC organisms (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Streptococcus pneumoniae ATCC 49619, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853). In addition, disk diffusion zone diameter QC limits were determined for apramycin, enrofloxacin, and premafloxacin by using E. coli ATCC 25922, P. aeruginosa ATCC 27853, and S. aureus ATCC 25923. The results from five or six participating laboratories produced >/=99.0% of MICs and >/=95.0% of the zone diameters within suggested guidelines. The NCCLS Subcommittee for Veterinary Antimicrobial Susceptibility Testing has recently approved these ranges for publication in the next M31 document.

Aminoglycosides↗

Evaluation of the Etest method for determining voriconazole susceptibilities of 312 clinical isolates of Candida species by using three different agar media.

Performance of the Etest for voriconazole susceptibility testing of 312 isolates of Candida spp. was assessed against that of the National Committee for Clinical Laboratory Standards (NCCLS) microdilution broth method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose (RPG), Casitone agar (CAS), and antibiotic medium 3 (AM3) agar and were read after incubation for 48 h at 35 degrees C. The Candida spp. isolates included C. albicans (n = 174), C. glabrata (n = 55), C. tropicalis (n = 31), C. parapsilosis (n = 39), C. krusei (n = 5), C. lusitaniae (n = 2), and C. guilliermondii (n = 6). The Etest results obtained using RPG correlated well with the reference MICs. Overall agreement ranged from 91% for C. glabrata to 100% for C. tropicalis, C. parapsilosis, C. guilliermondii, C. krusei, and C. lusitaniae. When CAS was used, agreement ranged from 80% for C. krusei to 100% for C. parapsilosis, C. guilliermondii, and C. lusitaniae. With AM3, agreement ranged from 58% for C. glabrata to 100% for C. lusitaniae and C. guilliermondii. The Etest method using RPG appears to be a useful method for determining voriconazole susceptibilities of Candida species.

Agar↗

Evaluation of the discriminatory powers of the Dienes test and ribotyping as typing methods for Proteus mirabilis.

A total of 63 clinical isolates of Proteus mirabilis collected over a 19-month period were typed by the Dienes test and ribotyping. Ribotyping was performed using the fully automated RiboPrinter Microbial Characterization System (Qualicon, Wilmington, Del.). Isolates that were indistinguishable by the Dienes test and/or ribotyping were characterized further by pulsed-field gel electrophoresis (PFGE). Most of the isolates represented unique strains as judged by the Dienes test and ribotyping. Forty isolates represented 40 different ribotypes and Dienes types. The remaining 23 isolates were grouped into 13 Dienes types, 12 ribotypes, and 14 PFGE types. The index of discrimination was 0.980 for the Dienes test, 0.979 for ribotyping, and 0.992 for PFGE. Both the Dienes test and ribotyping are useful methods for identifying individual strains of P. mirabilis. The Dienes test is simple, inexpensive, and easy to perform. It can be performed in virtually any laboratory and should be used in the initial epidemiologic characterization of P. mirabilis isolates.

Automation↗

Comparison of agar diffusion methodologies for antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Pseudomonas aeruginosa is the most common pathogen infecting the lungs of patients with cystic fibrosis (CF). Improved antimicrobial chemotherapy has significantly increased the life expectancy of these patients. However, accurate susceptibility testing of P. aeruginosa isolates from CF sputum may be difficult because the organisms are often mucoid and slow growing. This study of 597 CF isolates of P. aeruginosa examined the correlation of disk diffusion and Etest (AB BIODISK, Solna, Sweden) results with a reference broth microdilution method. The rates of interpretive errors for 12 commonly used antipseudomonal antimicrobials were determined. The disk diffusion method correlated well (zone diameter versus MIC) for all of the agents tested. However, for mucoid isolates, correlation coefficients (r values) for piperacillin, piperacillin-tazobactam, and meropenem were <0.80. The Etest correlation with reference broth microdilution results (MIC versus MIC) was acceptable for all of the agents tested, for both mucoid and nonmucoid isolates. Category interpretation errors were similar for the disk diffusion and Etest methods with 0.4 and 0.1%, respectively, very major errors (false susceptibility) and 1.1 and 2.2% major errors (false resistance). Overall, both agar diffusion methods appear to be broadly acceptable for routine clinical use in susceptibility testing of CF isolates of P. aeruginosa.

Agar↗

Oxazolidinones: a review.

The oxazolidinones represent a novel chemical class of synthetic antimicrobial agents. They exhibit an unique mechanism of protein synthesis inhibition and generally display bacteriostatic activity against many important human pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Linezolid, the oxazolidinone which has been selected for clinical development, has near complete oral bioavailability plus favourable pharmacokinetic and toxicity profiles. Results from experimental models of infection and phase II trials reveal linezolid to be highly active in vivo against infections due to many common gram-positive pathogens. The role of linezolid remains to be determined in phase III clinical trials, but it shows great promise as an alternative to glycopeptides and streptogramins to treat serious infections due to resistant gram-positive organisms. Further modification of the oxazolidinone nucleus may yield agents with even greater potency and with novel spectra of activity.

Acetamides↗