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R N Jones

Publications and source records attributed to R N Jones.

At least 127 records · Page 7Linked to original sources
PubMed2001

Evaluation of Etest method for determining caspofungin (MK-0991) susceptibilities of 726 clinical isolates of Candida species.

The performance of the Etest for testing the susceptibilities to caspofungin (MK-0991) of 726 isolates of Candida spp. was assessed against 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. MICs were determined by Etest for all 726 isolates with RPMI agar containing 2% glucose (RPG) and were read after incubation for 48 h at 35 degrees C. The Candida isolates included Candida albicans (n = 486), Candida glabrata (n = 96), Candida tropicalis (n = 51), Candida parapsilosis (n = 47), Candida krusei (n = 11), Candida lusitaniae (n = 2), and Candida guilliermondii (n = 33). In addition, a subset of 314 isolates were also tested by Etest using Casitone agar (CAS) and antibiotic medium 3 agar (AM3). The Etest results obtained using RPG correlated well with reference MICs. Overall agreement was 94% with RPG, 82% with CAS, and 79% with AM3. When RPG was used, agreement ranged from 79% for C. parapsilosis to 100% for C. krusei, C. lusitaniae, and C. guilliermondii. When CAS was used, agreement ranged from 0% for C. lusitaniae to 100% for C. glabrata. With AM3, agreement ranged from 0% for C. lusitaniae to 100% for C. guilliermondii. All three media supported growth of each of the Candida species. Etest results were easy to read, with sharp zones of inhibition. In most instances (75%) where a discrepancy was observed between the Etest and the reference method, the Etest MIC was lower. The Etest method using RPG appears to be useful for determining caspofungin susceptibilities of Candida species.

Anti-Bacterial Agents↗
PubMed2001

International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program.

A surveillance program (SENTRY) of bloodstream infections (BSI) in the United States, Canada, Latin America, and Europe from 1997 through 1999 detected 1,184 episodes of candidemia in 71 medical centers (32 in the United States, 23 in Europe, 9 in Latin America, and 7 in Canada). Overall, 55% of the yeast BSIs were due to Candida albicans, followed by Candida glabrata and Candida parapsilosis (15%), Candida tropicalis (9%), and miscellaneous Candida spp. (6%). In the United States, 45% of candidemias were due to non-C. albicans species. C. glabrata (21%) was the most common non-C. albicans species in the United States, and the proportion of non-C. albicans BSIs was highest in Latin America (55%). C. albicans accounted for 60% of BSI in Canada and 58% in Europe. C. parapsilosis was the most common non-C. albicans species in Latin America (25%), Canada (16%), and Europe (17%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (97 to 100% at < or =8 microg/ml). Likewise, 97 to 100% of these species were inhibited by < or =1 microg/ml of ravuconazole (concentration at which 50% were inhibited [MIC(50)], 0.007 to 0.03 microg/ml) or voriconazole (MIC(50), 0.007 to 0.06 microg/ml). Both ravuconazole and voriconazole were significantly more active than fluconazole against C. glabrata (MIC(90)s of 0.5 to 1.0 microg/ml versus 16 to 32 microg/ml, respectively). A trend of increased susceptibility of C. glabrata to fluconazole was noted over the three-year period. The percentage of C. glabrata isolates susceptible to fluconazole increased from 48% in 1997 to 84% in 1999, and MIC(50)s decreased from 16 to 4 microg/ml. A similar trend was documented in both the Americas (57 to 84% susceptible) and Europe (22 to 80% susceptible). Some geographic differences in susceptibility to triazole were observed with Canadian isolates generally more susceptible than isolates from the United States and Europe. These observations suggest susceptibility patterns and trends among yeast isolates from BSI and raise additional questions that can be answered only by continued surveillance and clinical investigations of the type reported here (SENTRY Program).

Antifungal Agents↗
PubMed2001

In vitro evaluation of BI 397, a novel glycopeptide antimicrobial agent.

BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL 62,476 (A40926), has excellent in vitro activity against a wide range of Gram-positive organisms. In this extensive study, 630 contemporary (1998-2000) Gram-positive isolates were selected from various resistance surveillance studies for their resistance patterns to fluoroquinolones, macrolides-lincosamides-streptogramins, beta-lactams and glycopeptide agents. The BI 397 spectrum of activity was similar to that of other glycopeptides with a MIC90 of < or =0.5 microg/ml for all tested isolates with the exception of vancomycin-resistant enterococci Van A; (MIC90, 32 microg/ml). BI 397 was more potent than vancomycin and teicoplanin against Staphylococcus aureus (2- to 8-fold), beta-haemolytic streptococci (equal to >16-fold), viridans group streptococci (equal to >32-fold), and Corynebacterium spp. including C. jeikeium (8- to >16-fold). BI 397 was also more active than quinupristin/dalfopristin against all Gram-positive organisms tested with the exception of oxacillin-susceptible S. aureus, against which it had equal activity. BI 397 has little activity against Haemophilus influenzae (MIC90, 64 microg/ml) or other Gram-negative bacilli (MIC90, >64 microg/ml). BI 397 exhibited bacteriostatic activity (like the vancomycin control) versus most species, but was bactericidal against tested Streptococcus pneumoniae. In vitro testing conditions with blood supplemented or free protein containing media elevated BI 397 MIC results, and the 30-microg disk seems acceptable for further disk diffusion test development. Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicoplanin-refractory coagulase-negative staphylococci.

Anti-Bacterial Agents↗
PubMed2001

In vitro evaluation of ertapenem (MK-0826), a long-acting carbapenem, tested against selected resistant strains.

Ertapenem (MK-0826) is a novel, long-acting parenteral carbapenem. The purpose of this in vitro study was to test ertapenem's activity against a collection of multiply-resistant strains of gram-positive and -negative bacteria isolated from locations worldwide, and to examine its bactericidal activity and ability to act in a synergistic manner in combination with other antimicrobial agents. Ertapenem was active against a variety of gram-negative pathogens, with particular potency noted for Escherichia coli and Klebsiella pneumoniae (MIC90s < or =0.015-0.5 microg/mL) including extended spectrum beta-lactamase producing strains. Less ertapenem activity was seen against Pseudomonas aeruginosa, especially ceftazidime-resistant strains (MIC50 16 microg/mL). Except for enterococci, ertapenem was active against most gram-positive species, including beta-haemolytic streptococci (MIC90 0.03 microg/mL; 100% susceptible), viridans group streptococci (MIC90 2 microg/mL; 98.1% susceptible), and penicillin-susceptible Streptococcus pneumoniae (MIC90 < or =0.015 microg/mL; 100% susceptible). Ertapenem was also very potent against Haemophilus influenzae (MIC90 0.25 microg/mL; 100% susceptible). Bactericidal action was observed versus staphylococci, E. coli, and K. pneumoniae, and at least an additive effect was detected against the majority of the strains tested when ertapenem was combined with ciprofloxacin or gentamicin. These results from testing 902 organisms indicate that ertapenem appears to be a promising broad-spectrum carbapenem with a possible role against some emerging resistant species.

Anti-Bacterial Agents↗
PubMed2001

Nuclear dispositions of subtelomeric and pericentromeric chromosomal domains during meiosis in asynaptic mutants of rye (Secale cereale L.).

The nuclear dispositions of subtelomeric and pericentromeric domains in pollen mother cells (PMCs) were tracked during meiosis in wildtype and two asynaptic mutants of rye (Secale cereale L.) by means of fluorescence in situ hybridization (FISH). Homozygotes for sy1 and sy9 non-allelic mutations form axial elements during leptotene of male meiosis, but fail to form synaptonemal complexes. Consequently, recombination is severely impaired, and high univalency is observed at metaphase I. Simultaneous FISH with pSc200 subtelomeric tandem repeat and CCS1 centromeric sequence revealed that at pre-meiotic interphase the two domains are in a bipolar Rabl orientation in both the PMCs and tapetal cells. At the onset of meiotic prophase, the subtelomeric regions in PMCs of wildtype and sy9 cluster into a typical bouquet conformation. The timing of this event in rye is comparable with that in wheat, and is earlier than that observed in other organisms, such as maize, yeast and mammals. This arrangement is retained until later in leptotene and zygotene when the pericentromeric domains disperse and the subtelomeric clusters fragment. The mutant phenotype of sy9 manifests itself during leptotene to zygotene, when the pericentromeric regions become distinctly more distended than in wildtype, and largely fail to pair during zygotene. This indicates that difference in the nature or timing of chromosome condensation in this region is the cause or consequence of asynapsis. By contrast, sy1 fails to form comparable aggregates of subtelomeric regions at leptotene in only half of the nuclei studied. Instead, two to five aggregates are formed that fail to disperse at later stages of meiotic prophase. In addition, the pericentromeric regions disperse prematurely at leptotene and do not associate in pairs at any subsequent stage. It is supposed that the sy1 mutation could disrupt the nuclear disposition of centromeres and telomeres at the end of pre-meiotic interphase, which could cause, or contribute to, its asynaptic phenotype.

Cell Nucleus↗
PubMed2001

Factors affecting the use of a telephone-based intervention for caregivers of people with Alzheimer's disease.

We investigated the usefulness of a computer-mediated interactive voice response (IVR) system integrated with voicemail to help family caregivers manage disruptive behaviours in people with Alzheimer's disease. The randomization procedure resulted in 49 caregivers being assigned to the intervention group and 51 to the control group. Using their ordinary telephone, the caregivers were linked to the four components of the IVR system: monitoring and counselling, an in-home support group, 'ask the expert', and a respite conversation. During an 18-month study, total system usage amounted to 55 min per user (SD 78, range 1-318). Half the participants used the system for at least 22 min, and 25% for at least 70 min. Participants made between one and 45 calls over the study period, averaging 11 calls (SD 12). Approximately half of the intervention group used the system regularly for two or more months. These 'adopters' were significantly older, more highly educated and reported a greater sense of management of the situation than 'non-adopters'. Adopters were much more likely than non-adopters to have been rated as highly proficient by the trainer following the technology training session. The IVR approach appealed to a subset of users. However, the overall preference was for human interaction.

Alzheimer Disease↗
PubMed2001

Resistance patterns among nosocomial pathogens: trends over the past few years.

Multiple surveillance studies have demonstrated that resistance among prevalent pathogens is increasing at an alarming rate, leading to greater patient morbidity and mortality from nosocomial infections. Among Gram-positive organisms, the most important resistant pathogens are methicillin- (oxacillin-)resistant Staphylococcus aureus, beta-lactam-resistant and multidrug-resistant pneumococci, and vancomycin-resistant enterococci. Important causes of Gram-negative resistance include extended-spectrum beta-lactamases (ESBLs) in Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis, high-level third-generation cephalosporin (Amp C) beta-lactamase resistance among Enterobacter species and Citrobacter freundii, and multidrug-resistance genes observed in Pseudomonas aeruginosa, Acinetobacter, and Stenotrophomonas maltophilia. In selecting an empiric treatment for a nosocomial infection, one should consider the prevalent resistance patterns. Antimicrobials used for the treatment of nosocomial infections should be effective against any likely resistant pathogens and should not further promote the development of resistance. Recent data suggest that because of ESBLs and high-level amp C beta-lactamase resistances, use of third-generation cephalosporins may be ineffective in many patients with nosocomial infections. In addition, use of these agents may allow overgrowth of inherently resistant enterococci. The role of fluoroquinolones in the empiric treatment of nosocomial infections is also being limited by new resistance patterns and increasing resistance levels. Available antimicrobials with good activity against many resistant pathogens include the carbapenems, piperacillin/tazobactam, and cefepime. In addition, several new agents with good activity against Gram-positive organisms are in development or have been recently released. Appropriate antimicrobial selection, surveillance systems, and effective infection-control procedures are key partners in limiting antimicrobial-resistant pathogen occurrence and spread.

Anti-Bacterial Agents↗
PubMed2001

Antimicrobial susceptibility of quinupristin/dalfopristin tested against gram-positive cocci from Latin America: results from the global SMART (GSMART) surveillance study.

Gram-positive cocci are important causes of both nosocomial and community-acquired infections, and antimicrobial resistance among these pathogens has become an important problem worldwide. Since resistance among these organisms can vary substantially by geographic location, we conducted a multicenter surveillance study with isolates from five Latin American countries (15 medical centers). Quinupristin/dalfopristin (formerly RP-59500) is a novel streptogramin combination with focused activity against Gram-positive cocci, many exhibiting emerging resistance. The in vitro activity of quinupristin/dalfopristin and 12 other antimicrobial agents were evaluated against 1,948 strains including Staphylococcus aureus (747 strains), coagulase-negative staphylococci (CoNS;446 strains), enterococci (429 strains), and various Streptococcus spp. (326 strains). Oxacillin resistance was observed in 41% of S. aureus (MIC, e; 13 mm) and 40% of CoNS (MIC, e; 18 mm). Vancomycin, teicoplanin, and quinupristin/dalfopristin (MIC(90), 0.25 - 1 mg/ml) remained effective against all strains, but cross-resistance was high among other tested drugs. The quinupristin/dalfopristin MIC(50) for Streptococcus pneumoniae and other streptococci was only 0.5 mg/ml (13% to 28% were penicillin-resistant; 12% to 22% were macrolide-resistant). Enterococci demonstrated variable inhibition by quinupristin/dalfopristin depending upon identification and the susceptibility testing method used. The demonstrated quinupristin/dalfopristin activity against Enterococcus faecium was confirmed, but potential species identification errors with various commercial systems continue to confuse susceptibility statistics, even though some strains of E. faecium confirmed by PCR-based or other molecular identification techniques did have quinupristin/dalfopristin MICs of >e; 4 microg/ml. Most important, glycopeptide-resistant enterococci are rapidly emerging in Latin America, and quinupristin/dalfopristin appears active against many of these isolates as well as having potency against nearly all staphylococci and streptococci tested at e; 16 mm. Comparisons to GSMART results from other continents show nearly identical quinupristin/dalfopristin activity for each Gram-positive species tested. These results define the role of quinupristin/dalfopristin in Latin American medical centers and provide a benchmark for future in vitro comparisons.

Anti-Bacterial Agents↗
PubMed2001

Method preferences and test accuracy of antimicrobial susceptibility testing: updates from the College of Amercian Pathologists Microbiology Surveys Program.

OBJECTIVE: To summarize the antimicrobial susceptibility testing results from the College of American Pathologists (CAP) Microbiology Surveys Program for 2000. Specifically, the frequency of tests used and the quantitative and qualitative (susceptibility category) accuracy were assessed. DESIGN: The CAP Microbiology Surveys challenged subscribers in 2000 with 3 well-characterized organisms for antimicrobial susceptibility testing in pure culture. Each laboratory was to use the test method and reporting procedures routinely applied to patient samples. The strains were National Committee for Clinical Laboratory Standards (NCCLS) quality control organisms with precisely defined antimicrobial susceptibility patterns and reproducibility. Results reported by participants (2685-2979/sample) were graded for categorical accuracy and quantitative performance by comparing reported minimal inhibitory concentrations (microg/mL) or zone diameters (mm) against quality control ranges published by the NCCLS. The appropriateness of reported drugs was determined in the context of the type and anatomic location of the infection. RESULTS: The tests most often used varied by the species of the organism and growth characteristics of the isolated strains. Nonfastidious, rapid-growing Surveys unknowns (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) were most often tested with commercial systems (MicroScan, 42.0%-42.4%; Vitek, 41.5%-43.0%) or with the standardized disk diffusion method (12.8%-13.9%). In contrast, fastidious species, such as Streptococcus pneumoniae (ATCC 49619), were predominantly tested by Etest (40.3%), followed by disk diffusion (27.6%) and MicroScan (23.2%). Categorical accuracy was essentially equal between dilution (98.9%) and diffusion (99.0%) methods. Among the minimal inhibitory concentration methods used to test penicillin against S pneumoniae, Etest method quantitative accuracy (96.3%) was greater than that of MicroScan (92.4%). Quantitative accuracy was greatest for dilution minimal inhibitory concentration methods, with more than 90% of results within NCCLS quality control ranges for nearly all reported antimicrobials. Reevaluations of quality control ranges may be needed for 4 to 7 agents, depending on method. Reporting errors were also detected in 2 areas: (1) reporting results for drugs not active at the site of infection and (2) reporting results for drugs tested with suboptimal methods without published NCCLS interpretive criteria. CONCLUSIONS: Antimicrobial susceptibility testing methods used in US laboratories were dominated by commercial products with relatively high accuracy (qualitative and quantitative). As available methods have become better suited to both fastidious and rapid-growing species, reporting errors have assumed a higher level of concern to the CAP Surveys in an effort to minimize prescription errors.

Anti-Bacterial Agents↗
PubMed2000

Nosocomial bloodstream infections caused by Acinetobacter species in United States hospitals: clinical features, molecular epidemiology, and antimicrobial susceptibility.

We examined the clinical and epidemiological features of nosocomial bloodstream infections (BSIs) caused by Acinetobacter species and observed from 1 March 1995 through 28 February 1998 at 49 United States hospitals (SCOPE National Surveillance Program). Acinetobacter species were found in 24 hospitals (49%) and accounted for 1.5% of all nosocomial BSIs reported. One hundred twenty-nine isolates were identified either as A. baumannii (n=111) or other Acinetobacter species (n=18). Patients with A. baumannii BSI, compared with patients with nosocomial BSI caused by other gram-negative pathogens, were more frequently observed in the intensive care unit (69% vs. 47%, respectively; P<.001; odds ratio [OR] 2.4; 95% confidence interval [CI] 1.6-3.7) and were more frequently receiving mechanical ventilation (58% vs. 30%, respectively; P<.001; OR 3.2; 95% CI 2.1-4.8). Crude mortality in patients with A. baumannii BSI was 32%. Molecular relatedness of strains was studied by use of polymerase chain reaction-based fingerprinting. Clonal spread of a single strain occurred in 5 hospitals. Interhospital spread of epidemic A. baumannii strains was not observed. The most active antimicrobial agents against A. baumannii (90% minimum inhibitory concentration values) were imipenem (1 mg/L; 100% of isolates susceptible), amikacin (8 mg/L; 96%), tobramycin (4 mg/L; 92%), and doxycycline (4 mg/L; 91%). Thirty percent of isolates were resistant to > or =4 classes of antimicrobials and were considered to be multidrug resistant.

Acinetobacter↗
PubMed2000

Fluoroquinolone-resistant Haemophilus influenzae: frequency of occurrence and analysis of confirmed strains in the SENTRY antimicrobial surveillance program (North and Latin America).

The incidence of fluoroquinolone-resistant (FQR) Haemophilus influenzae and Moraxella catarrhalis isolated from clinical specimens remains very rare, and the identification of such strains has been previously limited to case reports from diverse geographic locations. During the 1997 through 1998 SENTRY Antimicrobial Surveillance Program, four FQR-H. influenzae (0.13% of all strains) and one FQR-M. catarrhalis strains were identified and confirmed as having elevated MICs to > or =5 FQ class drugs. Among H. influenzae strains, MICs to marketed FQs were > or =0.12 microg/ml with ciprofloxacin MIC results > or =8-fold higher than wild type susceptible strains. The FQR-H. influenzae isolates were then compared with two previously reported strains that were determined to be identical using ribotyping and other molecular methods. In contrast, the SENTRY isolates were all genetically distinct and had mutations in parC and/or gyrA. Isolates having the lowest MIC elevations had a single mutation in gyrA, while isolates with higher MICs had at least one mutation in both studied genes. In general, the single gyr A mutations involved the same position but differed in the amino acid substitution (Ser84Leu or Phe or Ala). The isolates reported outside the SENTRY Program (controls) had an unusual mutation in par C (Gly82Asp) and two mutations in gyr A; producing the highest recorded FQR MICs. The FQR-M. catarrhalis strain was discovered in late 1997 and has been reported before. Although detection of these FQR isolates remains at <1% of all contemporary H. influenzae and M. catarrhalis isolates, surveillance programs will be an important detection method to determine the extent of emerging novel resistance patterns among clinically prevalent fastidious pathogens.

Aged↗
PubMed2000

Serious streptococcal infections produced by isolates resistant to streptogramins (quinupristin/dalfopristin): case reports from the SENTRY antimicrobial surveillance program.

The emergence and sustained prevalence of Gram-positive organisms resistant to antimicrobials has been of interest for over a decade. Quinupristin/dalfopristin (formerly RP 59500 or Synercid) is a new injectable streptogramin combination that has been reported to have activity against Gram-positive organisms, even those with documented MLS(B) resistance. However, the two case reports presented here illustrate three well-documented Streptococcus spp. strains (S. mitis, S. pneumoniae) to be resistant to quinupristin/dalfopristin (MICs at 3, 8, and 12 microg/ml) following referral as routine isolates in the SENTRY Antimicrobial Surveillance Program. The S. pneumoniae pleural fluid isolate was cross-resistant to erythromycin. Both bacteremic S. mitis strains were resistant to macrolides (erythromycin, azithromycin, clarithromycin), lincosamides (clindamycin), and fluoroquinolones. Patient histories indicated no prior use of MLS class antimicrobials for the S. mitis case, but the patient having the S. pneumoniae isolate did receive prior treatment of erythromycin and clindamycin. All isolates had modestly increased penicillin MICs of 0.12 microg/ml. The mode of resistance to quinupristin/dalfopristin was not evident (sat A-negative by PCR); and these cases illustrate the existence of streptogramin-resistant isolates before the introduction of this antimicrobial class into human clinical practice.

Adult↗
PubMed2000

Respiratory tract pathogens isolated from patients hospitalized with suspected pneumonia: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997).

Thirty-seven sentinel hospitals (29 in the United States [US]; eight in Canada) collected bacterial isolates from hospitalized patients with a diagnosis of pneumonia. The antimicrobial susceptibility patterns of these pathogens were determined to more than 60 agents (40 reported) using the reference broth microdilution method described by the National Committee for Clinical Laboratory Standards. The five most frequently recorded species among the 2757 isolates collected during the study were (no. tested/%): Staphylococcus aureus (632/22.9%), Pseudomonas aeruginosa (498/18. 1%), Haemophilus influenzae (284/10.3%), Klebsiella spp. (240/8.7%), and Streptococcus pneumoniae (213/7.7%). There was a significant difference in the susceptibility to antimicrobials between the US and Canada for S. aureus to oxacillin (50.1% versus 93.8% susceptible, respectively), gentamicin (78.7% versus 97.8%), and fluoroquinolones (49.5 to 53.0% versus 89.8 to 94.9%). Amikacin (92. 8% susceptible) was the most active antimicrobial agent against P. aeruginosa, and meropenem was the most potent beta-lactam. Against H. influenzae, most drugs retained a high level of activity, whilst against the S. pneumoniae, only the newer fluoroquinolones (gatifloxacin, levofloxacin, sparfloxacin) remained highly effective in vitro. Only two antimicrobial agents (imipenem and meropenem) were >99% active against the Klebsiella spp. and Enterobacter spp. isolated in this survey (possess extended spectrum beta-lactamases or hyperproduction of Amp C cephalosporins); cefepime (95.6-100.0% susceptible) was significantly more active than other cephalosporins tested. Clonal, epidemic outbreaks of multiply resistant strains were very rare in monitored hospitals. In conclusion, important differences exist between the US and Canada in the susceptibility patterns of some respiratory tract pathogens to commonly used antimicrobial agents with Canadian strains generally being more susceptible to currently available antimicrobial agents.

Anti-Bacterial Agents↗
PubMed2000

Comparison of oral immediate-release (IR) and extended-release (ER) metronidazole bactericidal activity against Bacteroides spp. using an in vitro model of infection.

We used an anaerobic infection model capable of simulating human serum pharmacokinetic parameters (C(max), C(min), half-life, and AUC) to compare the activity of oral immediate-release (IR) and extended-release (ER) MTZ formulations. Four oral regimens of MTZ plus a control regimen were simulated in the model: [i] (IR) 500 mg q8h, [ii] ER 750 mg q12h, [iii] ER 750 mg q24h, and [iv] ER 1500 mg q24h. Two clinical Bacteroides fragilis isolates (MICs 0.5, 4.0 microg/mL) and two non-fragilis Bacteroides isolates (MICs 0.5, 3 microg/mL) were studied. All four oral MTZ regimens exhibited rapid, bactericidal activity (> or =3-log(10) decrease from the starting inoculum) within 12 h against both fragilis and non-fragilis Bacteroides isolates. Overall, no appreciable difference in the rate of bacteria killing was noted among the four MTZ formulations against either B. fragilis isolates (P = 0.907, 0.737) or non-fragilis isolates (P = 0.809, 0.768). We conclude that ER MTZ dosed at 12 or 24-h intervals possesses equivalent bactericidal activity to standard IR MTZ dosed every eight hours against susceptible Bacteroides spp.

Administration, Oral↗
PubMed2000

Frequency of occurrence and antimicrobial susceptibility patterns for pathogens isolated from latin american patients with a diagnosis of pneumonia: results from the SENTRY antimicrobial surveillance program (1998).

The correct empiric choice of antimicrobial therapy in the treatment of pneumonia in hospitalized patients has established itself as a major therapeutic challenge to clinicians. Selection of an inappropriate antimicrobial agent could lead to increased rates of mortality and morbidity. Characteristics of pathogens responsible for this infection such as species prevalence, overall antimicrobial resistance rates, and mechanisms of detected resistance could serve as an invaluable resource to clinicians in making such therapeutic selections. This report addresses the aforementioned problems/needs by analysis of 712 strains isolated from the lower respiratory tract of patients hospitalized with a diagnosis of pneumonia in 10 Latin American medical centers in the SENTRY Antimicrobial Surveillance Program (1998). The four most frequently isolated pathogens (no/% of total) were: Pseudomonas aeruginosa (191/26.8%), Staphylococcus aureus (171/24.0%), Klebsiella spp. (86/12.1%), and Acinetobacter spp. (75/10.5%); representing nearly 75.0% of all isolates. More than 40 antimicrobial agents (23 reported) were tested against these isolates by reference broth microdilution methodology, and susceptibility profiles were established. The nonfermentative Gram-negative bacteria (P. aeruginosa and Acinetobacter spp.) exhibited high levels of resistance to the agents tested. Amikacin (77.5% susceptible) was the most active drug tested against P. aeruginosa 50.0% against the Acinetobacter spp. isolates. Based on published interpretive criteria, over 22.0% of the Klebsiella spp. and 12.5% of the Escherichia coli were classified as extended spectrum beta-lactamase (ESBL) producers. Of the cephalosporin class compounds tested against the Klebsiella spp. and E. coli isolates, cefepime demonstrated the highest rates of susceptibility (84.9% and 91.7%, respectively). This compound also fared well against the Enterobacter spp. isolates, inhibiting 88.2% of the isolates tested, many of which were resistant to ceftazidime and ceftriaxone. Resistance to oxacillin among the S. aureus isolates was nearly 50. 0%, with vancomycin, teicoplanin, and the streptogramin combination quinupristin/dalfopristin inhibiting all isolates. Several clusters of multiply resistant organisms were also observed, and further characterization by ribotyping and pulsed-field gel electrophoresis established possible patient-to-patient spread. The results of this study indicate that rates of resistance among respiratory tract pathogens continue to rise in Latin America, with specific concerns for the high prevalence of nonfermentative Gram-negative bacteria isolated, oxacillin resistance rates in S. aureus, and the epidemic dissemination of multiply-resistant strains in several medical centers. International surveillance programs (SENTRY) should assist in the control of escalating antimicrobial resistance in this geographic area.

Anti-Bacterial Agents↗
PubMed2000

Antimicrobial activity of advanced-spectrum fluoroquinolones tested against more than 2000 contemporary bacterial isolates of species causing community-acquired respiratory tract infections in the United States (1999).

In vitro activity of four newer fluoroquinolones (clinafloxacin, gemifloxacin, moxifloxacin, sitafloxacin) and an equal number control drugs in the same class (ciprofloxacin, grepafloxacin, levofloxacin, trovafloxacin) was determined by reference dilution tests against 2156 recent United States clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. All the fluoroquinolones demonstrated excellent in vitro activity against these pathogens. Streptococcus pneumoniae isolates were fully susceptible to clinafloxacin, sitafloxacin, and gemifloxacin at 0.5 microg/ml, and over 98% of sampled strains had MICs of </=1 microg/ml for grepafloxacin, moxifloxacin and trovafloxacin. Penicillin resistance did not influence the potency of the tested fluoroquinolones. All the isolates of H. influenzae and M. catarrhalis were inhibited by the investigational, as well as comparator fluoroquinolones at </=0.5 microg/ml, irrespective of their beta-lactamase producing abilities. In conclusion, the investigational fluoroquinolones demonstrated excellent activity against these major respiratory tract pathogens isolated in 1999, and some remain safe candidates for empiric therapy of community-acquired respiratory tract infections and selected infections in hospitalized patients.

Anti-Infective Agents↗
PubMed2000

In vitro activity of selected cephalosporins and erythromycin against staphylococci and pneumococci isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

The SENTRY Antimicrobial Surveillance Program employs a worldwide network of hospitals to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with nosocomial and community-acquired bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY data is to extract information on the current North American susceptibility patterns of pneumococci and oxacillin-susceptible staphylococci from the comprehensive SENTRY program database. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of 34 530 North American bacterial isolates tested during 1997 and 1998, 565 (1.6%) were oxacillin-susceptible, coagulase-negative staphylococci (CoNS). Cefazolin, cefepime, and ceftriaxone all had excellent activity against these CoNS (97.3%-99. 3% susceptible), and 90.4% were susceptible to ceftazidime. A total of 4404 isolates (12.8%) were oxacillin-susceptible Staphylococcus aureus. Overall, 98.9% to 99.2% were susceptible to cefazolin, cefepime, and ceftriaxone; ceftazidime did not have acceptable activity against these S. aureus. Streptococcus pneumoniae accounted for 1665 (4.8%) of North American SENTRY isolates. A total of 1212 isolates (72.8%) were fully susceptible to penicillin (MIC </= 0.06 microg/ml), 250 (15%) were penicillin intermediate (MIC 0.12-1 microg/ml), and 203 (12.2%) were penicillin resistant (MIC >/= 2 microg/ml). The rate of penicillin susceptibility was highest in Canada, and lowest in the South Central and South East regions of the United States. Cefepime, cefuroxime, ceftazidime, and erythromycin all demonstrated excellent efficacy (94%-99.8% susceptibility) against fully penicillin-susceptible isolates of S. pneumoniae. Among pneumococci with intermediate penicillin resistance, 88% were susceptible to cefepime, 92% to cefotaxime, and only 14% to ceftazidime. None of the antimicrobial agents in this analysis demonstrated adequate activity against fully penicillin-resistant pneumococci. In summary, the fourth-generation cephalosporin, cefepime, demonstrated consistently excellent efficacy against oxacillin-susceptible staphylococci and most pneumococci, and remains an appropriate choice for empiric therapy of serious infections.

Anti-Bacterial Agents↗