Biomedical subjects

R N Jones

Publications and source records attributed to R N Jones.

At least 181 records · Page 10Linked to original sources

PubMed2000

Activity of macrolides, lincosamines, streptogramins and fluoroquinolones against streptococcus pneumoniae and enterococci isolates from the western hemisphere: example of international surveillance (SENTRY antimicrobial surveillance program )in the development of new drugs.

Resistance among commonly isolated Gram-positive cocci have compromised the available therapeutic regimens and require structured monitoring at the local, regional, national, and international levels. Two popular treatment classes of antimicrobials (macrolides-lincosamines-streptogramins [MLS], fluoroquinolones) have been tested against 3, 049 isolates of Streptococcus pneumoniae and enterococci from the SENTRY Antimicrobial Surveillance program. The strains were obtained from clinical cases in hospitals in the United States, Canada, and six nations (10 medical centers )in Latin America. MLS and fluoroquinolone compounds had moderate activity against vancomycin-susceptible Enterococcus faecalis only (gatifloxacin, and trovafloxacin MIC(50), 0.5 microg/ml), and quinupristin/dalfopristin was potent only against E.faecium isolates (MIC(90), 1 microg/ml(-2) microg/ml). When tested against pneumococci, gatifloxacin, trovafloxacin, sparfloxacin, and quinupristin/dalfopristin (MIC(90), < or = 1 microg/ml)were most active among the newer drugs, but vancomycin and clindamycinn inhibited > or =99.8% and 84.7% to 99.1% of strains, respectively. These results from a global resistance monitoring program should encourage rapid drug development. Based on in vitro sensitivity testing, they indicate a promising role for the treatment of emerging resistant Gram-positive cocci. The clinical role for each new agent will depend on safety profiles, rates of administration, and other issues identified during development in the clinical trials process.

Amino Sugars↗

PubMed2000

Perspectives on the development of new antimicrobial agents for resistant gram-positive pathogens.

There is great public and professional concern related to antimicrobial resistance, especially among Gram-positive pathogens associated with high morbidity and mortality. Penicillin-nonsusceptible Streptococcus pneumoniae, glycopeptide resistant enterococci, and oxacillin-resistant (MRSA) or vancomycin-intermediate (VISA) Staphylococcus aureus isolates continue to escalate in occurrence leading to the widespread use of empiric combination regimens. Newer, often novel, agents seem necessary to combat these pathogens. Among these, quinupristin/dalfopristin (Synercid), evernimicin or SCH 27899 (Ziracin), and linezolid (Zyvax) have the highest potency, widest spectrum, and most clinical experience. Among the quinolones (gatifloxacin, gemifloxacin, moxifloxacin), gatifloxacin is closest to clinical use and appears safe based on initial trial reports. Several broad-spectrum beta-lactams ("fourth-generation" cephalosporins, carbapenems) are expected to be used with increasing frequency as a result of the emerging high rates of specific beta-lactamases that compromise the use of ceftriaxone, ceftazidime, and many beta-lactamase inhibition/ penicillin combinations. Among these agents, cefepime and meropenem are the most potent and broadest in clinical application in their respective classes. Physicians must stay informed about drug development and antimicrobial resistance by using results from local surveillance programs. When these data are unavailable, physicians should consider the use of national or global monitoring systems (SENTRY) to direct empiric antimicrobial selection.

Anti-Bacterial Agents↗

PubMed2000

Prevalence of antimicrobial resistance among respiratory tract isolates in Latin America: results from SENTRY antimicrobial surveillance program (1997-98).

One thousand seventy-three bacterial isolates were collected from patients with community acquired respiratory tract infections (CARTI) in 11 Latin American centers (7 countries) during 1997 and 1998. They were tested against numerous antimicrobial agents by the reference broth microdilution method as part of the ongoing multinational SENTRY Antimicrobial Surveillance Program. Among Streptococcus pneumoniae (553 isolates), approximately 61% were susceptible to penicillin. There was a great variation of the penicillin susceptibility rates among participating countries. The highest susceptibility rates were found in Argentina (76.7%) and Brazil (71.9%), while the lowest rate of penicillin susceptibility was detected in Mexico (33.3%). High level resistance to penicillin and resistance to cefotaxime were observed in nearly 10% of the isolates. The newer quinolones, levofloxacin (MIC(90) 2 microg/mL) and gatifloxacin (MIC90 0.5 microg/mL), were active against 100% of the isolates tested. Among the other non-beta-lactams drugs tested, the rank order of susceptibility against the pneumococci was: chloramphenicol (93.9%)>clindamycin (93.2%)> azithromycin (89.1%) > clarithromycin (88.7%)>tetracycline (78.5%)> trimethoprim/sulfamethoxazole (55.7%). The percentage of Haemophilus influenzae (361 isolates) isolates resistant to amoxicillin was 12. 7% (beta-lactamase positive). Among Moraxella catarrhalis (159 isolates) isolates, only 8.2% were susceptible. Clavulanic acid restored the activity of amoxicillin against both species. Trimethoprim/sulfamethoxazole was active against only 59.5% of H. influenzae, while susceptibility to this compound among M. catarrhalis was 96.1%. All other compounds tested were active against>95% of H. influenzae and M. catarrhalis isolates. These species were susceptible to levofloxacin (MIC90 < or = 0.5 microg/mL for both) and gatifloxacin (MIC90 < or = 0.03 microg/mL for both) with very low MICs. Our results indicate that penicillin resistance rates are particularly high among pneumococci in some countries. The newer fluoroquinolones show an excellent potency and spectrum against pathogens causing community acquired respiratory infections in Latin America.

Anti-Bacterial Agents↗

PubMed2000

Detection of emerging resistance patterns within longitudinal surveillance systems: data sensitivity and microbial susceptibility. MYSTIC Advisory Board. Meropenem Yearly Susceptibility Test Information Collection.

Communicating information from antimicrobial resistance surveillance study data to microbiologists and physicians can be challenging. Large amounts of data, commonly reaching millions of MICs or zone diameter endpoints, must be analysed and condensed to easily-read tables or figures. Furthermore, data must not be prejudged relative to susceptibility categories, because of the diverse nature of interpretive criteria available internationally. An attempt must be made to present results of all surveillance studies in a mode that can be reinterpreted for immediate use in different geographical areas, or used to compare future data with relative ease and high accuracy. Such data displays require peer-reviewed journals to permit greater numbers of more complex tables to present results. The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) study is a year-on-year global surveillance programme in medical centres where meropenem is available for use. We have developed a presentation strategy that expands the long-term clinical value of MYSTIC results. In addition to statistical parameters, tables of cumulative percentages or numbers of strains inhibited at each tested antimicrobial concentration will be presented. Alternative figures (Finland-o-grams) could also be used, but these generally lack precise extractable rates and require more journal space. Regardless of study design, promotion of this presentation philosophy enhances any surveillance study's value to each reader or user and facilitates application to locally appropriate interpretations. The widespread use of these analysis and presentation principles as benchmarks by various resistance studies and networks is strongly encouraged, particularly by investigations across international boundaries.

Anti-Bacterial Agents↗

PubMed2000

MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from the Americas: resistance implications in the treatment of serious infections. MYSTIC Study Group (Americas).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme aims to provide in vitro surveillance data for geographically diverse institutions where meropenem is available for use. The in vitro activity of meropenem and eight comparator antimicrobial agents against 2340 significant pathogens obtained in 1999 was assessed and compared in 14 study centres in Brazil, Mexico and the USA. Isolates were further characterized for production of extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases and carbapenemases. Carbapenems demonstrated their broad spectrum and potency, inhibiting > or = 95% of all isolates irrespective of the geographical region or centre type. The overall order of activity of the nine agents tested against all pathogens in 1999 was meropenem (96%) > imipenem (95%) > cefepime (92%) > gentamicin (89%) > piperacillin/tazobactam (88%) > ceftazidime = tobramycin (86%) > cefotaxime (84%) > ciprofloxacin (83%). Thus far, the results from the Americas indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients. In contrast, other ESBLs, fluoroquinolones and aminoglycosides have lost activity in many institutions as a result of the selection of strains producing ESBLs or having AmpC and other resistance determinants. Carbapenem resistance was observed rarely and at a prevalence similar to those reported in earlier studies. Carbapenems appear to be a continuing reliable option for the treatment of serious nosocomial infection.

Americas↗

PubMed1999

The impact of antimicrobial resistance: changing epidemiology of community-acquired respiratory-tract infections.

Current surveillance data and mechanisms of resistance for the three most common bacteria infecting the respiratory tract are reviewed. Many pathogens, once susceptible to available antimicrobials, are now demonstrating high levels of resistance to commonly prescribed antimicrobial agents for the treatment of respiratory-tract infections. The three most common respiratory-tract pathogens, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, all exhibit high-level resistance to one or a number of agents, including penicillin, ampicillin, erythromycin, tetracycline, and first-generation cephalosporins. To determine the prevalence of resistance in these organisms, surveillance programs have begun tracking the emergence of antimicrobial resistance in the United States and worldwide. Data recovered from several national surveillance studies should help guide decisions about empirical therapeutic treatment.

Community-Acquired Infections↗

PubMed1999

Comparative in vitro activity of gatifloxacin against Stenotrophomonas maltophilia and Burkholderia species isolates including evaluation of disk diffusion and E test methods.

The in vitro activity of gatifloxacin, a new fluoroquinolone, was compared to that of five other fluoroquinolones against 105 Stenotrophomonas maltophilia isolates and 52 Burkholderia spp. isolates. The gatifloxacin MICs were determined using the broth microdilution method and the E test (AB Biodisk, Sweden); these methods were compared for test accuracy, and 5 microg disk zone diameters were compared for interpretive accuracy using the standardized disk diffusion method. In terms of potency, gatifloxacin was most similar to sparfloxacin and trovafloxacin against Stenotrophomonas maltophilia (MIC50, 0.5-1 mg/l) and Burkholderia spp. (MIC50, 1-2 mg/l). This activity was greater than that of ciprofloxacin, levofloxacin or ofloxacin (MIC50, > or = 2 mg/l) against Stenotrophomonas maltophilia isolates but comparable to that of levofloxacin against the Burkholderia spp. (60% susceptible at < or = 2 mg/l). The E test results compared well with the reference dilution test results (81-97% at +/- 1 log2 dilution). The disk diffusion test using previously suggested breakpoints for other bacteria (> or = 18 mm or < or = 2 mg/l for susceptible and < or = 14 mm or > or = 8 mg/l for resistant) also performed well, at > 90% categorical agreement. The activity of gatifloxacin is comparable to that of other newer quinolones against isolates of Stenotrophomonas maltophilia and Burkholderia spp., and susceptibility testing using simple qualitative and quantitative methods appears to function well with these drug/organism combinations.

Anti-Infective Agents↗

PubMed1999

Spectrum and antimicrobial activity of alexomycin (PNU-82, 127), a peptide compound projected for use in animal health.

Alexomycin (PNU-82, 127) is a thiopeptide antimicrobial complex intended for veterinary practice that belongs to a series of cyclic peptides produced by Streptomyces arginensis. MICs against selected routine and fastidious clinical isolates of animal and human origin were determined by broth microdilution or agar dilution reference methods. Alexomycin was active against Gram-positive pathogens such as oxacillin-susceptible and -resistant Staphylococcus aureus and coagulase-negative staphylococci (260 strains; MIC90, 0.5 microgram/mL), as well as Enterococcus species (95 strains; MIC90, 0.25 to 0.5 microgram/mL), and generally inactive against Gram-negative aerobes. Alexomycin had more potent activity against Streptococcus bovis (MIC90, 0.12 microgram/mL), S. agalactiae (MIC90, 0.12 microgram/mL), Corynebacterium species (MIC90, 0.06-0.12 microgram/mL), and Listeria monocytogenes (MIC90, 0.5 microgram/mL). Alexomycin activity was limited against Bacillus species (MIC90, 1 microgram/mL), Neisseria meningiditis (MIC90, 2 micrograms/mL), Haemophilus influenzae (MIC90, 8 micrograms/mL), Moraxella catarrhalis (MIC90, 16 micrograms/mL), and Campylobacter jejuni (MIC90, 32 micrograms/mL). This thiopeptide complex was also found to be stable at low concentrations (0.015-32 micrograms/mL) in Mueller-Hinton broth for up to 24 h, possesses static antimicrobial activity and did not produce resistant mutants after multiple passages at subinhibitory drug concentrations. Alexomycin seems to have potential for use as a feed additive to increase feed efficiency and promote growth in poultry and swine as well as other applications against Gram-positive pathogens.

Animals↗

PubMed1999

Comparative antimicrobial activity of gatifloxacin tested against Campylobacter jejuni including fluoroquinolone-resistant clinical isolates.

Campylobacter jejuni is an important pathogen that causes gastroenteritis, as well as other disease states such as meningitis and septic arthritis. In this study, the Etest (AB BIODISK, Solna, Sweden) results were compared to a reference agar dilution method using gatifloxacin, a new 8-methoxyfluoroquinolone. A total of 53 strains of C. jejuni initially isolated from patients in California and Mexico were tested. Results demonstrated a high correlation (r = 0.88) between the two utilized in vitro dilution methods. In addition, gatifloxacin activity was compared to that of ciprofloxacin, metronidazole, amoxicillin, erythromycin, chloramphenicol, gentamicin, tetracycline, and trimethoprim/sulfamethoxazole using the Etest. Gatifloxacin (MIC90, 4 micrograms/ml) was approximately eight- to 16-fold more potent than ciprofloxacin (Mic90, > 32 micrograms/ml), a commonly used fluoroquinolone for Campylobacter infections. Eight strains highly resistant to ciprofloxacin (MIC90, > 32 micrograms/ml) were tested for cross resistance against the newer fluoroquinolones (gatifloxacin, levofloxacin, trovafloxacin) and the rank order of potency was: gatifloxacin (MIC50, 16 micrograms/ml) > trovafloxacin = levofloxacin (MIC50, > 32 micrograms/mL). However, only 25% ciprofloxacin-resistant strains were inhibited by < or = 1 microgram/mL of gatifloxacin or trovafloxacin. These results for gatifloxacin against C. jejuni strains must be further assessed in the context of in vivo trials before the clinical role of this new fluoroquinolone can be determined. The Etest appears to be a simple and precise susceptibility test method for testing C. jejuni isolates against fluoroquinolones and other alternative therapeutic agents.

Anti-Bacterial Agents↗

PubMed1999

Comparative antimicrobial activity of gatifloxacin tested against Streptococcus spp. including quality control guidelines and etest method validation. Quality Control Study Group.

Gatifloxacin (formerly AM-1155 or CG 5501) is a new 8-methoxy fluoroquinolone with enhanced activity against Gram-positive cocci, especially Streptococcus pneumoniae and other streptococci. Recent clinical strains (599 isolates) were tested against gatifloxacin, three comparison fluoroquinolones, and penicillin by the reference broth microdilution, Etest (AB BIODISK, Solna, Sweden) and standardized disk diffusion methods (5 micrograms gatifloxacin disk). Gatifloxacin (MIC90, 0.5 microgram/ml) activity was generally comparable to that of trovafloxacin (MIC90, 0.25 microgram/ml), or sparfloxacin (MIC90, 0.5 microgram/ ml) and markedly superior to ofloxacin (MIC90, 2-4 micrograms/ml) against the streptococci. Rates of penicillin non-susceptibility were 41.9, 38.0, and 16.2% for S. pneumoniae (301 strains), viridans group streptococci (150 strains), and beta-haemolytic streptococci (148 strains). Etest results correlated well (95.7-100.0% +/- one log2 dilution) with the reference MIC results, but Etest tended to have elevated gatifloxacin MIC results compared to the broth microdilution method for the highly resistant isolates (MICs, > 2 micrograms/ml). Gatifloxacin disk zone diameters correlate well to reference MICs for all streptococci and proposed interpretive criteria (susceptible at < or = 1 microgram/ml or > or = 18 mm, and resistant at > or = 4 micrograms/ml or < or = 14 mm) did not produce discords between method results (absolute agreement). A nine laboratory quality control (QC) study conforming to the National Committee for Clinical Laboratory Standards (NCCLS) Guideline M23-T3 studied S. pneumoniae ATCC 49619 and gatifloxacin. Proposed ranges for QC of NCCLS tests were 0.12-0.5 microgram/ml for the broth microdilution test and 24-31 mm for the disk diffusion method. These reported results indicate that gatifloxacin was a potent fluoroquinolone with extensive activity against streptococcal isolates. In vitro test methods to measure this activity appear accurate and comparable; and QC guidelines have been established for routine clinical laboratory use pending approval by the NCCLS and the Food and Drug Administration (FDA).

Anti-Infective Agents↗

PubMed1999

Gatifloxacin (AM-1155, CG 5501) susceptibility testing interpretive criteria and quality control guidelines for dilution and disk (5-microgram) diffusion methods. The Quality Control Study Group.

Gatifloxacin (formerly AM-1155 and CG5501), a new 8-methoxy fluoroquinolone, has an expanded spectrum of activity against Gram-positive cocci and some anaerobic bacteria. This compound was tested against 600 recent clinical strains of rapidly growing aerobic species to establish susceptibility testing interpretive criteria for the reference broth microdilution and standardized disk (5-microgram) diffusion methods of the National Committee for Clinical Laboratory Standards (NCCLS). These strains included 285 Enterobacteriaceae (17 species), 165 staphylococci, 49 enterococci, and 101 nonfermentative Gram-negative bacilli. Based on achievable serum levels with projected gatifloxacin dosing regimens, MIC break points of < or = 2 micrograms/mL (> or = 18 mm) for susceptibility and > or = 8 micrograms/mL (< or = 14 mm) for resistance were selected. The absolute agreement between tests was 94.3% with no very major false-resistant errors. The quality control ranges (MIC and zone diameters) for the NCCLS recommended strains were determined in a nine-laboratory NCCLS protocol as follows: Escherichia coli ATCC 25922 = 0.008-0.03 microgram/mL and 31-37 mm; Enterococcus faecalis ATCC 29212 = 0.12-1 microgram/mL; Pseudomonas aeruginosa ATCC 27853 = 0.5-2 micrograms/ml and 21-27 mm; Staphylococcus aureus ATCC 25923 = 27-33 mm and S. aureus ATCC 29213 = 0.03-0.12 microgram/mL. Gatifloxacin appears to be a promising new fluoroquinolone with acceptable susceptibility testing methods for routine clinical laboratory use.

Anti-Infective Agents↗

PubMed1999

Antimicrobial activity and spectrum of SCH27899 (Ziracin) tested against gram-positive species including recommendations for routine susceptibility testing methods and quality control. Quality Control Study Group.

SCH27899 is an oligosaccharide, everninomicin antibiotic with activity primarily against Gram-positive pathogens. The activity of SCH27899 was evaluated against 360 routine clinical isolates by the broth microdilution (BMD), agar dilution (AD), disk diffusion (DD), and Etest (AB BIODISK, Solna, Sweden) methods. In addition, results from a nine center SCH27899 quality control (QC) trial were used to establish QC ranges. SCH27899 MICs for 330 Gram-Positive strains, including multiply-resistant staphylococci and enterococci, ranged from 0.015 to 1 microgram/ml with MIC90s of 0.12 to 0.5 microgram/ ml. SCH27899 had no measurable activity against the 30 selected Gram-negative strains tested (MICs, > 256 micrograms/ml), with the exception of Moraxella catarrhalis MICs, 0.12 microgram/ ml). Etest MICs for SCH27899 correlated well with AD and BMD results with > 90% of MICs within +/- one log2 dilutions of the reference test results. Three disk concentrations (2.5-, 5-, 10-microgram) of SCH27899 were evaluated, but minimal difference of zone diameters between disk drug contents was observed (+/- 2 mm). SCH27899 disk zone diameters correlated poorly with reference MICs due to small zone diameters (range, 11 to 22 mm) attributed to poor diffusion through agar mediums, a product of this compound's high molecular weight and solubility. The use of the DD method for SCH27899 was not recommended. The proposed MIC quality assurance limits for SCH27899 using Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 was 0.06 to 0.25 microgram/ml for both QC strains and methods. SCH27899 appears to be a eveminomicin-derivative widely active against important Gram-positive cocci, and in vitro dilution testing methods would be preferred for clinical use, validated by the recommended MIC control ranges cited in this report.

Aminoglycosides↗

PubMed1999

Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines.

SB-265805 (formerly LB20304) is a novel C-7 pyrrolidine-substituted naphthyridone that has a broad spectrum of activity, especially against Gram-positive cocci. SB-265805 activity was compared with ciprofloxacin, grepafloxacin, moxifloxacin, sparfloxacin, and penicillin against 599 Streptococcus spp. isolated recently from more than 30 medical centers in North and South America. These included 70 isolates with decreased susceptibility to recently released fluoroquinolones (levofloxacin MIC, > or = 4 micrograms/mL). All strains were tested by reference microdilution methods in lysed horse blood-supplemented Mueller-Hinton broth. Sixteen percent of 148 beta-haemolytic streptococci (strains of gr. B and C) were not susceptible to penicillin, whereas 38% and 42% of viridans group streptococci and Streptococcus pneumoniae were resistant to penicillin, respectively. SB-265805 potency against 301 pneumococci (MIC90, 0.06 microgram/mL) was fourfold more active than moxifloxacin and was > or = eightfold more potent than other quinolones. Against beta-haemolytic streptococci, SB-265805 and moxifloxacin were the most active (MIC90, 0.06 and 0.25 microgram/mL, respectively), whereas sparfloxacin, grepafloxacin, and ciprofloxacin (MIC90, 0.5-1 microgram/mL) were less potent. SB-265805 MICs versus viridans group streptococci (MIC90, 0.12 microgram/mL) were fourfold lower than sparfloxacin or grepafloxacin, and twofold more active than moxifloxacin. A nine-laboratory quality control (QC) protocol conforming to NCCLS M23-T3 guidelines demonstrated a modal SB-265805 MIC of 0.016 microgram/mL for S. pneumoniae ATCC 49619 (proposed QC range, 0.008 to 0.03 microgram/mL). The SB-265805 disk (5-microgram) QC range was 28-34 mm (97.3% of qualifying results). In general, SB-265805 in vitro activity against Streptococcus species was superior to sparfloxacin, grepafloxacin, and moxifloxacin and markedly greater than ciprofloxacin. This degree of antimicrobial potency warrants further investigation of this newer drug for its potential human clinical application against streptococcal infections.

Anti-Infective Agents↗

PubMed1999

Antimicrobial activity of SCH27899 (Ziracin), a novel everninomicin derivative, tested against Streptococcus spp.: disk diffusion/etest method evaluations and quality control guidelines. The Quality Control Study Group.

To combat the increasing rates of penicillin resistance among pneumococci and viridans group streptococci, new Gram-positive active agents are needed to avoid the overuse of vancomycin. SCH27899 is an everninomicin derivative with strong activity against glycopeptide-resistant enterococci, oxacillin-resistant staphylococci, and penicillin-resistant streptococci. This study tests the in vitro activity of SCH27899 against 304 strains of streptococci and evaluates the quality of the agar dilution, broth microdilution, disk diffusion, and Etest methods for this antimicrobial agent. Quality-control (QC) ranges for SCH27899 are also proposed. SCH27899 broth microdilution MICs among the penicillin-susceptible and -resistant streptococci tested ranged from < or = 0.008-0.5 microgram/mL. Organism groups with their respective MIC90s were as follows: Streptococcus pneumoniae (100 strains) and beta-haemolytic streptococci (70 strains), 0.12 microgram/mL; Streptococcus bovis (10 strains), 0.25 microgram/mL; and viridans group streptococci (124 strains), 0.5 microgram/mL. Etest SCH27899 MICs correlated well with broth microdilution MICs (92% +/- one log2 dilution, 98% +/- two log2 dilutions). Agar dilution SCH27899 MICs correlated well with broth microdilution MICs, but a shift toward slightly higher agar dilution MICs was attributed to difficulties in reading trailing endpoints with this method. Three concentrations (2.5, 5, and 10 micrograms) of SCH27899 were used for the disk diffusion method with small inhibition zone diameters (range, 11 to 19 mm) and limited variation between diameters (+/- 2 mm) as a result, both products of this compound's high molecular weight and poor diffusion through agar mediums. Proposed control ranges for SCH27899 when testing S. pneumoniae ATCC 49619 from a nine-center (30 tests per center) quality-control trial are < or = 0.016 to 0.032 microgram/mL for Etest, and 0.008 to 0.032 microgram/mL for broth microdilution tests from an earlier study. Because of the limited diffusion ability and bacteriostatic nature of SCH27899, MICs should be read at 80% of inhibition with agar in vitro systems (Etest, agar dilution), and the disk diffusion method is not recommended.

Aminoglycosides↗

PubMed1999

Epidemiologic trends in nosocomial and community-acquired infections due to antibiotic-resistant gram-positive bacteria: the role of streptogramins and other newer compounds.

The Gram-positive cocci have clearly re-emerged as important pathogens world-wide in the past two decades. Staphylococci, including the coagulase-negative staphylococci and Staphylococcus aureus, and the enterococci account for approximately one-third of all blood stream infections and as much as 50% of nosocomial blood stream infections. Although Streptococcus pneumoniae is often considered a community-acquired pathogen, it is also an important cause of nosocomial infection. The hallmark of these Gram-positive pathogens is increasing resistance to available antimicrobial agents. Of particular note is resistance to glycopeptides (vancomycin and teicoplanin), aminoglycosides (high-level), and penicillins among the enterococci (especially E. faecium), resistance to penicillinase-resistant penicillins (oxacillin and methicillin) and fluoroquinolones (ciprofloxacin and ofloxacin) among staphylococci, and resistance to penicillin, other beta-lactams and macrolides among the pneumococci. The recent detection of decreased susceptibility to vancomycin among S. aureus is also quite ominous. In many instances the ability of the clinical laboratory to accurately characterize these resistant isolates is suboptimal, further compounding the problem. Increased understanding of resistance mechanisms and correlations of resistance genes with the phenotypic expression of resistance has allowed for modifications and improvements of reference susceptibility tests and interpretive breakpoints. New compounds for effective therapy of infection with multi-resistant Gram-positive species are clearly needed. To this end, the streptogramin combination, quinupristin/dalfopristin, has demonstrated significant activity against oxacillin-resistant staphylococci, penicillin-resistant streptococci, and vancomycin-resistant E. faecium. Other candidate drugs including Gram-positive active fluoroquinolones (clinafloxacin, grepafloxacin, moxifloxacin, gatifloxacin, and trovafloxacin) and novel compounds such as the everninomicin derivatives (SCH27899), ketolides, and oxazolidinones (linezolid) have been shown to be active against these organisms and are under rapid clinical development.

Anti-Bacterial Agents↗

PubMed1999

Survey of blood stream infections attributable to gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Program. SENTRY Participants Group.

The SENTRY Antimicrobial Surveillance Program was established in January, 1997 to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a network of sentinel hospitals in the United States (30 sites), Canada (eight sites), Latin America (10 sites), and Europe (24 sites). During the first 12-month study period (January to December, 1997), a total of 9519 blood stream infections (BSI) were reported by SENTRY participants in the U.S. (6150), Canada (1727), and Latin America (1642). The Gram-positive cocci, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), enterococci, and streptococci accounted for 53.9% (5131 infections) of all BSI (56.5% U.S., 55.7% Canada, and 42.9% Latin America). The staphylococci, Enterococcus spp., S. pneumoniae, beta-hemolytic streptococci, and viridans group streptococci accounted for 6 of the top 11 BSI pathogens in the U.S. and Canada, whereas only S. aureus (1st), CoNS (3rd), and Enterococcus spp. (9th) were among the top 11 pathogens in Latin American hospitals. The results of this survey affirm the importance of Gram-positive cocci as causes of BSI in both North America and Latin America and demonstrate that important antimicrobial resistance exists among isolates of staphylococci, streptococci, and enterococci from all three geographic regions. This includes oxacillin-resistance among S. aureus (26.9% U.S., 29.2% Latin America, and 4.0% Canada) and CoNS (71.5% U.S., 68.4% Latin America, and 65.6% Canada), penicillin resistance among viridans group streptococci (48.5% U.S., 45.1% Canada, and 33.3% Latin America) and pneumococci (36.1% U.S., 27.5% Canada, and 65.6% Latin America), high-level resistance (HLR) to aminoglycosides among enterococci (27.2 to 70.1% U.S., 33.3 to 75.7% Canada and 16.7 to 51.5% Latin America), and macrolide resistance among beta-hemolytic streptococci (12.4 to 14.2% U.S., 10.5 to 12.3% Canada, and 0.0 to 4.0% Latin America), viridans group streptococci (32.4 to 39.7% U.S., 22.5-35.2% Canada, and 20.0% Latin America), and pneumococci (10.0 to 10.6% U.S., 9.8-10.8% Canada, and 9.4-18.7% Latin America). BSI isolates of Gram-positive cocci from the U.S. and Latin America were considerably more resistant than those from Canada. New agents with Gram-positive activity will be essential for optimal treatment of BSI attributable to Gram-positive cocci in both North and Latin America.

Anti-Bacterial Agents↗

PubMed1999

Characteristics of pathogens causing urinary tract infections in hospitals in North America: results from the SENTRY Antimicrobial Surveillance Program, 1997.

Urinary tract infection (UTI) is common and involves pathogens with changing susceptibility patterns. The SENTRY Antimicrobial Surveillance Program evaluates international pathogen incidence patterns to detect and manage the emergence of resistant strains. We describe the antimicrobial resistance patterns among 1617 pathogens recovered from UTIs during the third-quarter of 1997 in North America (United States and Canada), as part of this worldwide program. The isolates were tested against more than 50 antimicrobial agents (20 reported) by reference broth microdilution methods, and selected isolates were characterized by pulsed-field gel electrophoresis (PFGE) and automated ribotyping. The five most frequently isolated species were Escherichia coli (48.6%), Enterococcus spp. (13.7%), Klebsiella spp. (12.0%), Pseudomonas aeruginosa (6.2%), and Enterobacter spp. or Proteus mirabilis (3.8% each). For each nation, imipenem and cefepime produced the widest spectrum of coverage among the beta-lactams and amikacin was best among the aminoglycosides. For Gram-negative species, high resistance among beta-lactam antimicrobial agents was noted especially for various penicillins against E. coli (37.9% to 42.8%) and for the cephalosporins tested against enterococci (99.4% and 100%). Approximately 7.0% of enterococci in the USA were vancomycin-resistant (88% with Van A). P. aeruginosa provided the most consistent levels of resistance, but the following agents were most active against these organisms: amikacin (96.6 to 97.4% susceptible), tobramycin (89.5 to 100.0%), piperacillin/tazobactam (89.5 to 100.0%), piperacillin (89.5 to 96.6%), imipenem (89.7 to 92.1%), cefepime (77.6 to 89.7%), and ceftazidime (82.9 to 86.2%). E. coli (2.2 to 2.7%), K. pneumoniae (6.2 to 6.4%), and a single Enterobacter cloacae strain produced extended-spectrum beta-lactamases; and five other Enterobacter spp. were likely to have expressed chromosomally mediated (Amp C) Stably derepressed cephalosporinases with associated resistance to ceftazidime (16.7 to 21.2% resistance). These data demonstrated that several UTI isolates in SENTRY hospitals have high levels of resistance to various classes of antimicrobial agents with little evidence of clonal dissemination.

Anti-Bacterial Agents↗

PubMed1999

Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States.

National surveillance of blood stream infections (BSI) attributable to Candida spp. has been limited to date. Recent studies have suggested in increase in the proportion of BSI attributable to non-Candida albicans species and have also raised concerns regarding the emergence of antifungal resistance among Candida spp. The increased utilization of broad-spectrum antifungal agents and the recognition of Candida spp. as prominent pathogens with the potential for developing antifungal resistance, emphasize the need for ongoing surveillance of antifungal susceptibility patterns. In this investigation trends in species distribution and susceptibility to fluconazole among BSI isolates of Candida spp. referred to our laboratory by United States hospitals were evaluated over the 7-year period from 1992 to 1998. A total of 1579 BSI isolates from more than 50 medical centers were processed. Overall, C. albicans accounted for 52% of isolates followed by C. glabrata (18%), C. parapsilosis (15%), C. tropicalis (11%), and C. krusei (2%). The proportion of BSI isolates that were C. albicans ranged from 45% in 1992 to 60% in 1998. Among the non-C. albicans isolates, C. glabrata succeeded C. parapsilosis as the most common species beginning in 1995. Overall, the susceptibility of all Candida species (C. albicans plus all other species) to fluconazole remained stable (MIC90, 16 micrograms/mL). The fluconazole MIC90 for C. albicans was 0.5-2.0 micrograms/ml for all years studied except 1995 (8.0 micrograms/mL) and was 1.0 microgram/mL overall. The present study suggests a continued prominent role of C. albicans as a cause of BSI, and a constant level of susceptibility of Candida BSI isolates to fluconazole over 7 years. These data should serve as a baseline for future surveillance efforts for anti-fungal agents tested against yeast BSI isolates.

Antifungal Agents↗